MOLECULES, COMPOSITIONS AND METHODS FOR TREATMENT OF CANCER

INCORPORATION OF SEQUENCE LISTING

The material in the accompanying sequence listing is hereby incorporated by reference into this application. The accompanying sequence listing text file, name JHU4140_1WO_Sequence_Listing, was created on ______, and is ______ kb. The file can be accessed using Microsoft Word on a computer that uses Windows OS.

BACKGROUND OF THE INVENTION
Field of the Invention

The present invention relates generally to the field of multifunctional fusion proteins to counteract immune dysfunction in the tumor microenvironment and more specifically to compositions and methods employing such fusion proteins (either alone or in combination regimens) for treatment of cancer.

Background Information

Genetic mutations accruing from the inherent genomic instability of tumor cells present neo-antigens that are recognized by the immune system. Cross-presentation of tumor antigens at the immune synapse between antigen-presenting dendritic cells and T lymphocytes can potentially activate an adaptive antitumor immune response that is mediated by CD4 T-helper cells (T_H1) and CD8⁺ cytotoxic effector cells, and sustained by tumor-reactive central memory T cells¹. However, tumors continuously evolve to counteract and ultimately defeat such immune surveillance by co-opting and amplifying mechanisms of immune tolerance to evade elimination by the immune system. This prerequisite for tumor progression is enabled by the ability of cancers to produce multiple immunomodulatory factors that create a tolerogenic or dysfunctional immune cell microenvironment. The tumor microenvironment is enriched with multiple cytokines and ligands that act in concert to alter the recruitment, differentiation, activation, or effector function of immune cells (T cells, macrophages, dendritic cells, NK cells), thereby resulting in key signatures of immune dysfunction that enable tumorigenesis, tumor progression, and metastases: (1) Immune tolerance: via expression of ligands that suppress the activation or function of immune cells (T cells, NK cells, macrophages, DCs) and skew their differentiation toward an immuno-inhibitory phenotype (e.g. regulatory T cells, Tregs); (2) Tumor promoting inflammation; via expression of ligands that skew the differentiation of immune cells toward a phenotype (e.g. TH17 cells; M2 macrophages) that in turn, express cytokines and ligands which promote multiple tumor cell proliferation/survival, tumor angiogenesis, and metastases. As such the key signatures of immune dysfunction in the tumor microenvironment (TME) (immune tolerance and tumor-promoting inflammation) involve complex multipronged cross-talk between tumor cells and tumor-infiltrating immune cells. The key molecular determinants of such deleterious cross-talk involve interactions between ligands expressed on tumor cells and their cognate receptors on tumor-infiltrating immune cells (T cells, macrophages, DC, NK cells), or conversely, ligands expressed on immune cells (e.g. Tregs, TH17 cells) and their cognate receptors on tumor cells or tumor-associated cells (e.g endothelial cells, CAFs).

Efforts to counteract immune dysfunction in the TME are currently stymied or limited by the following key therapeutic challenges: (1) The plethora of ligands that act independently or in concert to create the dysfunctional TME. As such, therapeutic agents that address a specific molecular determinant fails to counteract other redundant or orthogonal ligands that are concurrently or adaptively upregulated to create the dysfunctional immune signature (immune tolerance or tumor-promoting inflammation); (2) The complexity and promiscuity of ligand-receptor interactions that operate in the TME. Tumor cell-immune cell cross-talk involves multiple autocrine and paracrine ligand-receptor interactions (in cis and trans) that maintain the abnormal phenotype of both tumor cells and tumor-infiltrating immune cells. Many ligands interact with more than one receptor, and in some instances the same ligand can have disparate, opposing, or bidirectional effects when it interacts with different receptors on a T cell; the effect of a ligand-receptor interaction on an immune cell is further influenced by other ligand-receptor signals that may simultaneously operate in the TME; (3) Stifling the molecular determinants of immune tolerance (for e.g. specific immune checkpoints, such as T cell co-inhibitory molecules) may fail to counteract, or even counterproductively exacerbate, ligand-receptor(s) that cause tumor-promoting inflammation and angiogenesis; (4) The selective or preferential localization of therapeutic molecules to the TME is required to effectively disrupt autocrine/paracrine ligand-receptor interactions that are hyperactive in the localized microenvironment of a tumor cell, tumor-infiltrating immune cell, or tumor-infiltrating endothelial cell.

The present invention describes novel multifunctional molecules that are designed to address these therapeutic challenges that limit current cancer therapy. The molecules of the invention are designed to simultaneously counteract one or more of the key determinants of the key signatures of the tumor microenvironment: (1) Immune cell suppression and immune tolerance; (2) tumor-promoting inflammation; (3) elevated neoangiogenesis. These signatures are ubiquitous hallmarks of cancers that are key determinants of tumor progression as well as their resistance to current anticancer therapies. Since immune dysfunction and angiogenesis are also the Achilles' heel of cancers, the multifunctional molecules of the invention may provide effective immunotherapeutic strategies. The invention also describes methods of treatment of cancers that attempt to address these therapeutic challenges. These methods include but are not limited to methods that utilize novel multifunctional molecules of the invention for cancer immunotherapy, either alone or in combination regimens.

SUMMARY OF THE INVENTION

The present invention is based on the seminal discovery that fusion proteins comprising at least one ligand binding sequence of the extracellular domain of a protein and a targeting moiety are effective at treating various diseases and disorders.

The molecules of the invention are fusion proteins comprising at least one ligand-binding sequence of the extracellular domain (ECD, or “ligand trap”) or fragment thereof of a naturally-occurring protein, or modified version or fragment thereof.

In some embodiments, the fusion proteins of the invention comprise a targeting polypeptide to which one or more ECDs are fused. “X” is a molecule that is specifically bound by the targeting polypeptide. “Y” is a ligand-binding sequence of an extracellular domain, or fragment thereof. In some embodiments, the fusion proteins of the invention have the structure “anti-{X}-{Y}”, where the ligand-binding sequence of the extracellular domain Y is fused to the targeting polypeptide. In some embodiments, the targeting polypeptide is an antibody that comprises at least one heavy chain and one light chain. In some embodiments, Y is fused to the C terminus of the light chain of the antibody. In other embodiments, Y is fused to the C terminus of the heavy chain of the antibody. In some embodiments, Y is fused to the N terminus of the light chain of the antibody. In other embodiments, Y is fused to the N terminus of the heavy chain of the antibody.

In some embodiments, the fusion proteins of the invention have the structure “anti-{X}-{Y}-{Z}”, where Y and Z are fused to the polypeptide that binds X. In some embodiments, Y is fused to the C terminus of the heavy chain of the antibody and Z is fused to the C terminus of the light chain of the antibody. In other embodiments, Y is fused to the C terminus of the light chain of the antibody and Z is fused to the C terminus of the heavy chain of the antibody. In some embodiments, Y is fused to the N terminus of the heavy chain of the antibody and Z is fused to the N terminus of the light chain of the antibody. In other embodiments, Y is fused to the N terminus of the light chain of the antibody and Z is fused to the N terminus of the heavy chain of the antibody.

In some embodiments, an ECD of the invention may be modified in one or more of the following ways: (1) substitution or deletion of residues that are not necessary for ligand binding, (2) substitution of residues to remove N-linked glycosylation sites, (3) substitution, addition, or deletion of residues to increase affinity to one or more of its cognate ligands, (4) substitution, addition, or deletion of residues to improve the expression of the fusion protein, (5) substitution, addition, or deletion of residues to allow for site-specific conjugation of drug conjugates, (6) substitution, addition, or deletion of residues to decrease the specificity of the ligand trap to one or more of its cognate ligands while maintaining or increasing its specificity to other cognate ligands, (7) fusion of non-continuous domains of the same ECD, (8) fusion of domains from different isoforms of the same ECD, (9) fusion of domains from different members of the same ECD family. In some embodiments, any of these modifications refer to the same ECD if they result in a sequence that maintains 90%, 95%, 98%, or 99% sequence identity to a ligand-binding sequence of the ECD.

In some embodiments, the fusion proteins comprise two ECDs (ECD #1, ECD #2) fused together. In some embodiments, the fusion protein additionally comprises a Fc domain. In some embodiments, the fusion protein additionally comprises a linker. In some embodiments, the structure of the fusion protein is N (terminus)-ECD #1-ECD #2-C (terminus). In other embodiments, the structure is N-ECD #2-ECD #1-C. In other embodiments, the structure is N-ECD #1-linker-ECD #2-C or N-ECD #2-linker-ECD #1-C. In other embodiments, the structure is N-ECD #1-Fc-ECD #2-C or N-ECD #2-linker-ECD #1-C. In other embodiments, the structure is N-ECD #1-Fc-linker-ECD #2-C, or N-ECD #2-Fc-linker-ECD #1-C.

In one aspect, component parts of the fusion proteins of the invention are fused via a flexible linker. In a further aspect, the flexible linker comprises the polypeptide sequence (GGGGS)n where n is between 1 and 10. In another aspect, the flexible linker is selected from the following list: (GGGGS)3 (SEQ ID NO: 200), (GGGGS)4 (SEQ ID NO: 201), waldo1999 (SEQ ID NO: 202), bird1988-1 (SEQ ID NO: 203), bird1988-2 (SEQ ID NO: 204). In one aspect, a linker may be used to fuse an ECD to a targeting polypeptide. In another aspect, a linker may be used to fuse one ECD to another. In another aspect, a linker may be used to fuse an ECD to the C terminus of the CH3 region of the heavy chain of an Fc polypeptide.

In various embodiments, the fusion proteins of the invention comprise one or more of the following ECDs: (1) a ligand-binding sequence of an extracellular domain of TGFbR (e.g., TGFbRII ECD), or fragment thereof. In one aspect, this ECD binds TGFb1, TGFb2, and/or TGFb3; (2) a ligand-binding sequence of an extracellular domain of PD-1 (e.g., PD1 ECD), or fragment thereof. In one aspect, this ECD binds PD-L1 and/or PD-L2. In one embodiment, this ligand trap has one or more amino acid substitutions which increase its affinity for PD-L1 and/or PD-L2; (3) a ligand-binding sequence of an extracellular domain of VEGFR (e.g., VEGFR1, VEGFR2, VEGFR3), or fragment thereof, or a fusion of VEGF-binding sequences of one or more VEGFR extracellular domains (e.g., VEGFR1 domain 2 fused to VEGFR2 domain 3). In one aspect, this ECD binds VEGFA, VEGFB, VEGFC, and/or PIGF; (4) a ligand-binding sequence of an extracellular domain of TIM-3 (e.g., TIM3 ECD), or fragment thereof, or a hypoglycosylated variant of TIM-3, or fragment thereof. In one aspect, this ECD binds CEACAM1, CEACAM5, phosphatidyl-serine, and/or Galectin-9; (5) a ligand-binding sequence of an extracellular domain of SIRPa (e.g., SIRPa-ECD), or fragment thereof; or a hypoglycosylated variant of SIRPa, or fragment thereof. In one aspect, this ECD binds CD47; (6) a ligand-binding sequence of an extracellular domain of B- and T-lymphocyte attenuator (BTLA ECD) or fragment thereof, or a hypoglycosylated variant of BTLA or fragment thereof. In one aspect, this ECD binds herpesvirus entry mediator (HVEM); (7) a ligand-binding sequence of an extracellular domain of SIGLEC10 or fragment thereof, or a hypoglycosylated variant of SIGLEC10 or fragment thereof. In one aspect, this ECD binds CD24.

In one aspect, the targeting polypeptide (TP) comprises an antigen-binding domain of an immunoglobulin, antibody, bispecific or multispecific antibody, antibody fragment, single chain variable fragment (scFv), bivalent or multivalent scFv, Affimer, a ligand-binding sequence from the extracellular domain (ECD) of a receptor, or Fc-containing polypeptide. In certain aspects, the targeting polypeptide is an antibody.

In some embodiments, the targeting polypeptide is an antibody and this antibody is fused to one or more ECDs. In such cases, the fusion protein comprising an antibody and one or more ECDs may be referred to as an “antibody-ligand trap”, or “ALT”, which are used interchangeably.

In some embodiments, this targeting polypeptide binds a tumor-associated antigen or tumor antigen. In one embodiment, a “tumor-associated antigen” is a molecule whose expression is elevated on tumor cells. In one embodiment, the tumor-associated antigen is a growth factor receptor or a growth factor. In some embodiments, the growth factor or growth factor receptor may be selected from the following list: EGFR, EGFRvIII, HER2, HER3, PDGF, PDGFR, HGF, HGFR, IGF, IGF1R, VEGF, VEGFR, TGFb, TGFbR, FGF, FGFR.

In one embodiment, the fusion protein of the invention comprises a targeting polypeptide that specifically binds a tumor cell surface molecule. In some embodiments, the targeting polypeptide binds one of the following targets: CA125, CA19-9, CD30, CEACAM5, CEACAM1, CEACAM6, DLL3, DLL4, DPEP3, EGFR, EGFRvIII, GD2, HER2, HER3, HGF, IGF1R, IL13Ra2, LIV-1, LRRC15, MUC1, PRLR, PSCA, PSMA, PTK7, SEZ6, SLAMF7, TF, cMet, claudin, mesothelin, nectin4, uPAR, GPNMB, CD79b, CD22, NaPi2b, SLTRK6, STEAP1, MUC16, CD37, GCC, AGC-16, 5T4, CD70, TROP2, CD74, CD27L, Fra, CD138, CA6.

In some embodiments, the targeting polypeptide binds an antigen overexpressed by a hematologic malignancy. In some embodiments, the targeting polypeptide binds an antigen overexpressed by multiple myeloma. In some embodiments, the targeting polypeptide binds CD38, SLAMF7, or BCMA. In some embodiments, the targeting polypeptide is an antibody selected from the following list: MEDI2228; CC-99712; belantamab; Gemtuzumab (anti-CD33 mAb). In some embodiments, the antibody binds CD20. In some embodiments, the targeting polypeptide binds rituximab (chimeric murine/human anti-CD20 mAb); Obinutuzumab (anti-CD20 mAb); Ofatumumab (anti-CD20 mAb); Tositumumab-I131 (anti-CD20 mAb); Ibritumomab tiuxetan (anti-CD20 mAb). In some embodiments, the targeting polypeptide binds CD19. In some embodiments, the antibody binds CD30, or CD22. In some embodiments, the targeting polypeptide binds an antigen overexpressed by leukemia. In some embodiments, the targeting polypeptide binds CD33.

In the case that the targeting polypeptide is a bispecific antibody (bsAb), it may be an obligate or non-obligate bsAb. In some embodiments, one of the targets of the bsAb is CD3. In one aspect, the bsAb may be a CrossMab or a BiTE. Examples of bsAbs that may be used as targeting polypeptides of the fusion proteins of the invention include the following: CD3×B7-H3 (e.g., orlotamab), CD3×BCMA (e.g., AMG420, AMG701, EM801, JNJ-64007957, PF-06863135, REGN5458), CD3×CD19 (e.g., A-319, AFM11, AMG562, blinatumomab), CD3×CD20 (e.g., mosunetuzumab, plamatomab, REGN1979, CD20-TCB), CD3×CD33 (e.g., AMG330, AMG673, AMV-564, GEM333), CD3×CD38 (e.g., AMG424, GBR1342), CD3×CEA (e.g., Cibisatamab), CD3×EGFRvIII (e.g., AMG596), CD3×EpCAM (e.g., A-337, catumaxomab, removab), CD3×FLT3 (e.g., AMG427), CD3×GPC3 (e.g., ERY974), CD3×gpA33 (e.g., MGD007), CD3×GPRC5D (e.g., JNJ-64407564), CD3×HER2 (e.g., GBR1302, M802, RG6194), CD3×MUC16 (e.g., REGN4018), CD3×P-Cadherin (e.g., PF-06671008), CD3×PSMA (e.g., AMG160, MOR209, pasotuxizumab), CD3×SSTR2 (e.g., tidutamab), CD40×MSLN (e.g., ABBV-428), PD-1×ICOS (e.g., Xmab23104), or PD-L1×4-1BB (e.g., MCLA-145), or CTLA-4×PD-1.

In one embodiment, the fusion protein of the invention comprises a targeting polypeptide that specifically binds a “don't eat me” ligand or receptor that inhibits the function of macrophages, dendritic cells, or other innate immune cells. “Don't eat me” ligands expressed by cells bind their cognate receptor on a macrophage, dendritic cell, or other innate immune cell to inhibit phagocytosis. Tumor cells take advantage of this anti-phagocytic mechanism and overexpress “don't eat me” ligands in order to inhibit innate immune cell antitumor activity. In some embodiments, the targeting polypeptide binds CD47, SIRPa, CD31, CD24, SIGLEC10, or LILRB1.

In one embodiment, the fusion protein of the invention comprises a targeting polypeptide that specifically binds a T cell inhibitory receptor (TCIR), a T cell inhibitory receptor ligand (TCIR ligand), a T-cell co-inhibitory molecule, or a T cell co-stimulatory molecule.

In an additional aspect, the antibody is an antagonist of a TCIR, TCIR ligand, or T cell co-inhibitory molecule. In an additional aspect, the targeting moiety polypeptide specifically binds one or more of the following molecules: Cytotoxic T lymphocyte associated antigen-4 (CTLA-4, CD152), Programmed Death-1 protein (PD-1), Programmed death ligand-1 (PD-L1), Programmed death ligand (PD-L2), B7-H3 (CD276), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), Carcinoembryonic antigen-related cell adhesion molecule (CEACAM), V domain Ig suppressor of T cell activation (VISTA), V-set and immunoglobulin domain containing 8 (VSIG8), B and T lymphocyte attenuator (BTLA), Herpesvirus Entry Mediator (HVEM), CD160, T cell Ig and ITIM domain (TIGIT), PVRIG, CD226, CD96, Lymphocyte activation gene-3 (LAG-3).

In another aspect, the targeting polypeptide is an agonist of a T cell co-stimulatory molecule. In one aspect, the targeting polypeptide is an antibody that binds a T cell co-stimulatory molecule as an agonist. In another aspect, the targeting polypeptide is the extracellular domain of a native agonist ligand of a T cell co-stimulatory molecule. In an additional aspect, the targeting polypeptide specifically binds one of the following molecules: 4-1BB (CD137), Inducible T-Cell Costimulator (ICOS), OX-40 (CD134), Herpesvirus Entry Mediator (HVEM), glucocorticoid-induced TNFR-related protein (GITR), CD40, CD30, DNAM, or CD27.

In one embodiment, the fusion protein of the invention comprises a targeting polypeptide that specifically binds a cytokine or cytokine receptor. In a preferred embodiment, the cytokine/cytokine receptor interaction contributes to immune tolerance and/or promotion of tumor-promoting inflammation. In some embodiments, the cytokine or cytokine receptor are selected from the following: IL-17, IL-17R, IL-23, IL-23R, IL-6, IL-6R, IL-1, IL-1R, IL-10, IL-10R, TGFb, or TGFbR.

In one embodiment, the fusion protein of the invention comprises a targeting polypeptide that specifically binds a ectonucleotidase. In some embodiments, the ectonucleotidase is CD39 or CD73.

In one embodiment, the invention comprises fusion proteins comprising targeting polypeptides wherein the targeting polypeptide is an antibody fused to one or more ECDs. In one aspect, the targeting polypeptide is an antibody-drug conjugate (ADC). In one aspect, the antibody is conjugated to one or more cytotoxic agents. In some embodiments, the cytotoxic agent causes immunogenic cell death. In some embodiments, the cytotoxic agent causes genotoxic cell death.

The cytotoxic agent conjugated to the targeting polypeptide antibody may be any agent that induces cell death. In various embodiments, the cytotoxic agent may be selected from, but is not limited to, the following list: (1) maytansinoid (DM1), (2) calcheamicin, (3) auristatin (e.g., monomethyl auristatin E (MMAE) or monomethyl auristatin F (MMAF)).

In some embodiments, the cytotoxic agent may be conjugated to cysteines. In other embodiments, the cytotoxic agent may be conjugated to lysines. In some embodiments, the cytotoxic agent may be conjugated via a cleavable linker. In some embodiments, the cytotoxic agent may be conjugated via a non-cleavable linker. In various embodiments, the cytotoxic agent may be linked to the targeting polypeptide antibody via a linker, which may be selected from, but is not limited to, the following list: (1) hydrazone, (2) SMCC (maleimide), (3) valine-citrulline, (4) 4AP, (5) maleimidocaproyl (mc), (6) maleimidomethyl cyclohexane-1-carboxylate (mcc). The linker may further comprise one or more spacers. In some embodiments, the spacer may be selected from thiol-reactive maleimidocaproyl spacer and p-amino-benzyloxycarbonyl spacer. In one embodiment, the cleavable linker is maleimidocaproyl-valyl-citrullinyl-p-aminobenzyloxycarbonyl (mc-val-cit-PABC).

In one embodiment, a tumor-targeted antibody is fused to one or more receptor extracellular domains and conjugated to one or more cytotoxic agents. In one embodiment, a fusion protein comprises a targeting polypeptide wherein the targeting polypeptide is an antibody-drug conjugate and the targeting polypeptide is fused to a ligand-binding sequence of a receptor ECD. In one aspect, the receptor ECD is fused to the heavy chain of the targeting polypeptide. In another aspect, the receptor ECD is fused to the light chain of the targeting polypeptide.

In one embodiment, a fusion protein comprises a targeting polypeptide wherein the targeting polypeptide is an antibody-drug conjugate and the targeting polypeptide is fused to a ligand-binding sequence of TGFbRII ECD, or a fragment thereof. In one embodiment, a fusion protein comprises a targeting polypeptide wherein the targeting polypeptide is an antibody-drug conjugate and the targeting polypeptide is fused to a ligand-binding sequence of PD1 ECD, or a fragment thereof. In one embodiment, a fusion protein comprises a targeting polypeptide wherein the targeting polypeptide is an antibody-drug conjugate and the targeting polypeptide is fused to a ligand-binding sequence of BTLA ECD, or a fragment thereof. In one embodiment, a fusion protein comprises a targeting polypeptide wherein the targeting polypeptide is an antibody-drug conjugate and the targeting polypeptide is fused to a ligand-binding sequence of TIM-3 ECD, or a fragment thereof. In one embodiment, a fusion protein comprises a targeting polypeptide wherein the targeting polypeptide is an antibody-drug conjugate and the targeting polypeptide is fused to a ligand-binding sequence of SIRPa ECD, or a fragment thereof. In one embodiment, a fusion protein comprises a targeting polypeptide wherein the targeting polypeptide is an antibody-drug conjugate and the targeting polypeptide is fused to a ligand-binding sequence of SIGLEC10 ECD, or a fragment thereof. In one embodiment, a fusion protein comprises a targeting polypeptide wherein the targeting polypeptide is an antibody-drug conjugate and the targeting polypeptide is fused to a ligand-binding sequence of VEGFR ECD, or a fragment thereof.

In various embodiments, the targeting polypeptide is an antibody-drug conjugate selected from: gemtuzumab ozogamicin, brentuximab vedotin, trastuzumab emtansine, inotuzumab ozogamicin, polatuzumab vedotin, enfortumab vedotin, trastuzumab deruxtecan, or sacituzumab govitecan.

In one embodiment, the fusion protein comprises anti-nectin-4 antibody fused to TGFbRII on the C-terminus of the heavy chain; and MMAE is conjugated to the antibody via a protease cleavable linker comprising maleimidocaproyl, valine-citrulline, and PABC. In one aspect, this fusion protein is anti-nectin4-TGFbRII (e.g., SEQ ID NOs: 265, 160). In one embodiment, the fusion protein comprises anti-nectin-4 antibody fused to BTLA on the C-terminus of the heavy chain; and MMAE is conjugated to the antibody via a protease cleavable linker comprising maleimidocaproyl, valine-citrulline, and PABC. In one aspect, this fusion protein is anti-nectin4-BTLA (e.g., SEQ ID NOs: 256, 160). In one embodiment, the fusion protein comprises anti-nectin-4 antibody fused to SIRPa on the C-terminus of the heavy chain; and MMAE is conjugated to the antibody via a protease cleavable linker comprising maleimidocaproyl, valine-citrulline, and PABC. In one aspect, this fusion protein is anti-nectin4-SIRPa (e.g., SEQ ID NOs: 264, 160). In one embodiment, the fusion protein comprises anti-nectin-4 antibody fused to PD1 on the C-terminus of the heavy chain; and MMAE is conjugated to the antibody via a protease cleavable linker comprising maleimidocaproyl, valine-citrulline, and PABC. In one aspect, this fusion protein is anti-nectin4-PD1 (e.g., SEQ ID NOs: 261, 160). In one embodiment, the fusion protein comprises anti-nectin-4 antibody fused to TIM3 on the C-terminus of the heavy chain; and MMAE is conjugated to the antibody via a protease cleavable linker comprising maleimidocaproyl, valine-citrulline, and PABC. In one aspect, this fusion protein is anti-nectin4-TIM3 (e.g., SEQ ID NOs: 266, 160). In one embodiment, the fusion protein comprises anti-nectin-4 antibody fused to SIGLEC10 on the C-terminus of the heavy chain; and MMAE is conjugated to the antibody via a protease cleavable linker comprising maleimidocaproyl, valine-citrulline, and PABC. In one aspect, this fusion protein is anti-nectin4-SIGLEC10 (e.g., SEQ ID NOs: 263, 160).

In one embodiment, the fusion protein comprises anti-HER2 antibody fused to TGFbRII on the C-terminus of the heavy chain; and DM1 is conjugated to the antibody via a linker comprising mcc. In one aspect, this fusion protein is anti-HER2-TGFbRII (e.g., SEQ ID NOs: 253, 55). In one embodiment, the fusion protein comprises anti-HER2 antibody fused to BTLA on the C-terminus of the heavy chain; and DM1 is conjugated to the antibody via a linker comprising mcc. In one aspect, this fusion protein is anti-HER2-BTLA (e.g., SEQ ID NOs: 244, 55). In one embodiment, the fusion protein comprises anti-HER2 antibody fused to TIM-3 on the C-terminus of the heavy chain; and DM1 is conjugated to the antibody via a linker comprising mcc. In one aspect, this fusion protein is anti-HER2-TIM3 (e.g., SEQ ID NOs: 254, 55). In one embodiment, the fusion protein comprises anti-HER2 antibody fused to PD1 on the C-terminus of the heavy chain; and DM1 is conjugated to the antibody via a linker comprising mcc. In one aspect, this fusion protein is anti-HER2-PD1 (e.g., SEQ ID NOs: 249, 55). In one embodiment, the fusion protein comprises anti-HER2 antibody fused to SIRPa on the C-terminus of the heavy chain; and DM1 is conjugated to the antibody via a linker comprising mcc. In one aspect, this fusion protein is anti-HER2-SIRPa (e.g., SEQ ID NOs: 252, 55). In one embodiment, the fusion protein comprises anti-HER2 antibody fused to SIGLEC10 on the C-terminus of the heavy chain; and DM1 is conjugated to the antibody via a linker comprising mcc. In one aspect, this fusion protein is anti-HER2-SIGLEC10 (e.g., SEQ ID NOs: 251, 55). In one embodiment, the fusion protein comprises anti-HER2 antibody fused to VEGFR on the C-terminus of the heavy chain; and DM1 is conjugated to the antibody via a linker comprising mcc. In one aspect, this fusion protein is anti-HER2-VEGFR (e.g., SEQ ID NOs: 255, 55).

The targeting polypeptide may be an Fc-containing polypeptide, and the CH3 region of the Fc may end with a terminal lysine. In some embodiments, the terminal lysine of the CH3 region of the Fc may be removed.

The fusion proteins of the invention are designed to counteract the molecular determinants that contribute to key signatures of the tumor microenvironment. The targeting polypeptide and/or ECDs counteract one or more of the key receptor/ligand interactions that underlie the following signatures in the TME.

The first signature of the tumor microenvironment is immune tolerance, characterized by the following: (a) suppression of the differentiation, maturation, and function of macrophages/dendritic cells mediated by “don't-eat-me” signals (e.g., CD47/SIRPa, CD31/CD31, SIGLEC10/CD24, LILRB1/MHC), immuno-inhibitory cytokines (e.g., TGFb/TGFbR), immuno-inhibitory molecules that signal via SHP1/SHP2 (e.g., PD1/PDL1/PDL2); (b) inhibition of tumor-relative T cell maturation, activation, and function mediated by T cell co-inhibitory molecules (e.g., PD1/PDL1/PDL2, CTLA-4, LAG3, BTLA/HVEM, TIGIT/PVRIG, TIM3/CEACAM, VISTA/VSIG8), and immunosuppressive molecules involved in Treg differentiation and/or function (e.g., CTLA-4, TGFb, CD39, CD73, IL-10, HVEM).

The second signature of the tumor microenvironment is tumor promoting inflammation, characterized by the following (a) induction and maintenance of TH17 cells in the TME mediated by cytokine/cytokine receptor interactions (e.g., IL-6/IL-6R, IL-23/IL-23R, TGFb/TGFbR, IL-1/IL-1R), (b) TH17 function & TH17/tumor cell/endothelial cell crosstalk mediated by cytokine/cytokine receptor interactions (e.g., TGFb/TGFbR, IL-17/IL-17R, VEGF/VEGFR), (c) promotion of neoangiogenesis mediated by cytokine/cytokine receptor interactions (e.g., VEGF/VEGFR, TGFb/TGFbR, IL-17/IL-17).

In some embodiments, the fusion proteins of the invention are preferentially localized to a component of the tumor microenvironment. In one aspect, the fusion protein comprises a targeting polypeptide and this targeting polypeptide binds a component of the tumor microenvironment to localize the fusion protein. In a further aspect, the fusion protein comprises a targeting polypeptide and this targeting polypeptide binds to a tumor cell surface molecule, or tumor-infiltrating immune cell surface molecule, thereby localizing the fusion protein to the immediate microenvironment of the targeted tumor cell, tumor-associated endothelial cell, or tumor-infiltrating T cell (e.g., Treg or TH17). In another aspect, an ECD of the fusion protein binds a component of the tumor microenvironment to localize the fusion protein. In a further aspect, an ECD of the fusion protein binds to a tumor cell surface molecule, or tumor-infiltrating immune cell surface molecule, thereby localizing the fusion protein to the immediate microenvironment of the targeted tumor cell, tumor-associated endothelial cell, or tumor-infiltrating T cell (e.g., Treg or TH17).

In addition to localizing the fusion protein, in some embodiments, the targeting polypeptide additionally exerts a function by neutralizing a receptor/ligand interaction that aggravates immune tolerance or tumor promoting inflammation. In other embodiments, the targeting polypeptide exerts a function by neutralizing a growth factor, growth factor receptor, or other molecule that promotes tumor cell survival, growth, or metastases. In other embodiments, the targeting polypeptide serves as an agonist that binds a T cell co-stimulatory molecule.

In various embodiments, the fusion proteins of the invention counteract VEGF in the tumor microenvironment.

In some embodiments, the fusion proteins of the invention comprise a targeting polypeptide that binds VEGF or VEGFR fused to one or more receptor ECDs. These receptor ECDs are preferably selected from the following: PD1 ECD, TIM-3 ECD, TGFbRII ECD, BTLA ECD, SIRPa ECD, SIGLEC10 ECD. In some embodiments, the targeting polypeptide that binds VEGF or VEGFR is an antibody. Exemplary embodiments include anti-VEGF-TGFbR (e.g., SEQ ID NOs: 370, 32); anti-VEGF-BTLA (e.g., SEQ ID NOs: 361, 32); anti-VEGF-SIGLEC10 (e.g., SEQ ID NOs: 368, 32); anti-VEGF-PD1 (e.g., SEQ ID NOs: 366, 32); anti-VEGF-SIRPa (e.g., SEQ ID NOs: 369, 32); anti-VEGF-TIM3 (e.g., SEQ ID NOs: 371, 32). In another embodiment, the fusion protein comprises antibody that binds VEGF or VEGFR fused to one receptor ECD on heavy chain and another receptor ECD fused on light chain. Exemplary embodiments include anti-VEGF-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 369, 363); anti-VEGF-TIM3-BTLA (e.g., SEQ ID NOs: 371, 367); anti-VEGF-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 361, 363); anti-VEGF-TGFbR-SIRPa (e.g., SEQ ID NOs: 370, 364); anti-VEGF-PD1-SIRPa (e.g., SEQ ID NOs: 366, 364); anti-VEGF-BTLA-TIM3 (e.g., SEQ ID NOs: 361, 365); anti-VEGF-TIM3-SIRPa (e.g., SEQ ID NOs: 371, 364); anti-VEGF-SIRPa-BTLA (e.g., SEQ ID NOs: 369, 367); anti-VEGF-SIRPa-TIM3 (e.g., SEQ ID NOs: 369, 365); anti-VEGF-TGFbR-SIGLEC10 (e.g., SEQ ID NOs: 370, 363); anti-VEGF-TGFbR-PD1 (e.g., SEQ ID NOs: 370, 362); anti-VEGF-PD1-SIGLEC10 (e.g., SEQ ID NOs: 366, 363); anti-VEGF-PD1-BTLA (e.g., SEQ ID NOs: 366, 367); anti-VEGF-TGFbR-TIM3 (e.g., SEQ ID NOs: 370, 365); anti-VEGF-SIGLEC10-BTLA (e.g., SEQ ID NOs: 368, 367); anti-VEGF-SIRPa-PD1 (e.g., SEQ ID NOs: 369, 362); anti-VEGF-BTLA-SIRPa (e.g., SEQ ID NOs: 361, 364); anti-VEGF-TGFbR-BTLA (e.g., SEQ ID NOs: 370, 367); anti-VEGF-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 371, 363); anti-VEGF-SIGLEC10-TIM3 (e.g., SEQ ID NOs: 368, 365); anti-VEGF-PD1-TIM3 (e.g., SEQ ID NOs: 366, 365); anti-VEGF-TIM3-PD1 (e.g., SEQ ID NOs: 371, 362); anti-VEGF-SIGLEC10-SIRPa (e.g., SEQ ID NOs: 368, 364); anti-VEGF-BTLA-PD1 (e.g., SEQ ID NOs: 361, 362); anti-VEGF-SIGLEC10-PD1 (e.g., SEQ ID NOs: 368, 362).

In other embodiments, the fusion proteins comprise a ligand-binding sequence of an extracellular domain of VEGFR (e.g., VEGFR ECD). In one aspect, the VEGFR ECD comprises Ig domain 2 from VEGFR1, fused to Ig domain 3 from VEGFR2. In one embodiment, the fusion protein comprises amino acids 103-204 of VEGFR1 fused to amino acids 206-308 of VEGFR2. In one embodiment, the fusion protein comprises the same domains of VEGFR1 and VEGFR2 as aflibercept. In some embodiments, the VEGFR ECD may be selected from the following list: SEQ ID NOS: 184; 185; 186. In a preferred embodiment, if the targeting polypeptide is an antibody, the VEGFR ECD is fused to the C terminus of the heavy chain of the antibody.

In one aspect, the fusion proteins of the invention comprise an antibody with VEGFR fused to the heavy chain of the antibody and another receptor ECD fused to the light chain of the antibody. This additional receptor ECD may be selected from BTLA, PD1, SIGLEC10, SIRPa, TIM3. Exemplary embodiments include anti-HER2-VEGFR-PD1 (e.g., SEQ ID NOs: 255, 245); anti-HER2-VEGFR-SIRPa (e.g., SEQ ID NOs: 255, 247); anti-HER2-VEGFR-BTLA (e.g., SEQ ID NOs: 255, 250); anti-HER2-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 255, 246); anti-HER2-VEGFR-TIM3 (e.g., SEQ ID NOs: 255, 248); and anti-EGFRvIII-VEGFR-BTLA (e.g., SEQ ID NOs: 243, 238); anti-EGFRvIII-VEGFR-TIM3 (e.g., SEQ ID NOs: 243, 236); anti-EGFRvIII-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 243, 234); anti-EGFRvIII-VEGFR-PD1 (e.g., SEQ ID NOs: 243, 233); anti-EGFRvIII-VEGFR-SIRPa (e.g., SEQ ID NOs: 243, 235).

Antitumor efficacy of CD47 blockade may be limited by disruption of TSP-1/CD47-dependent inhibition of VEGF and angiogenesis. In one embodiment, the fusion protein is a polypeptide comprising an antibody that targets CD47, wherein said antibody is fused to a VEGFR ECD. In one embodiment, this fusion protein is anti-CD47-VEGFR (e.g., SEQ ID NOs: 392, 22). In another aspect, the fusion protein comprises a VEGF-binding sequence from VEGFR ECD and a CD47-binding sequence from one or more extracellular domains of SIRPa (SIRPa ECD). In one embodiment, this fusion protein comprises SIRPa ECD and VEGFR ECD. In one embodiment, this fusion protein is SIRPa-Fc-VEGFR (e.g., SEQ ID NO: 552) or VEGFR-Fc-SIRPa (e.g., SEQ ID NO: 568).

In a further aspect, the fusion protein comprises VEGFR ECD, a polypeptide that inhibits the interaction between CD47 and SIRPa, and another receptor ECD. In some embodiments, this fusion protein comprises anti-CD47 mAb with VEGFR ECD fused to the heavy chain; and the other ECD fused to the light chain. Exemplary embodiments are anti-CD47-VEGFR-TIM3 (e.g., SEQ ID NOs: 392, 386); anti-CD47-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 392, 385); anti-CD47-VEGFR-BTLA (e.g., SEQ ID NOs: 392, 388); anti-CD47-VEGFR-PD1 (e.g., SEQ ID NOs: 392, 384).

In a further embodiment, the fusion protein is a tumor-targeted antibody-drug conjugate fused to VEGFR ECD. For example, the fusion protein may comprise enfortumab vedotin fused to VEGFR ECD. In a further embodiment, the fusion protein is a bispecific antibody that simultaneously binds a tumor cell and a T cell, fused to VEGFR ECD. For example, the fusion protein may comprise CD3×EGFRvIII (e.g., AMG596) fused to VEGFR ECD or CD3×CEA (e.g., cibisatamab) fused to VEGFR ECD or CD3×HER2 (e.g., GBR1302, M802, RG6194) fused to VEGFR ECD.

In some embodiments, the fusion protein comprises VEGFR ECD and a polypeptide that inhibits TGFb/TGFbR signaling. In some embodiments, the fusion protein comprises VEGFR ECD and anti-TGFb mAb, anti-TGFbR mAb, anti-LAP mAb, or anti-GARP mAb. In a further embodiment, the fusion protein may additionally comprise a receptor ECD fused to the light chain of the antibody. In some embodiments, the fusion protein is selected from anti-TGFb-VEGFR-SIRPa (e.g., SEQ ID NOs: 403, 396); anti-TGFb-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 403, 395); anti-TGFb-VEGFR-BTLA (e.g., SEQ ID NOs: 403, 399); anti-TGFb-VEGFR-TIM3 (e.g., SEQ ID NOs: 403, 397); anti-TGFb-VEGFR-PD1 (e.g., SEQ ID NOs: 403, 394).

TH17 cells produce IL-17 which is a key determinant of resistance to VEGF blockade. Additionally, endothelial cells on which VEGF act express IL-17R that responds to TH17-produced IL-17. In some embodiments, the fusion protein comprises VEGFR ECD and an antibody that binds and disables IL-17/IL-17R, IL-23/IL-23R, or IL-6/IL-6R. In some embodiments, the fusion protein is selected from the following: anti-IL17-VEGFR, anti-IL17R-VEGFR (e.g., SEQ ID NOs: 336, 63), anti-IL23-VEGFR (e.g., SEQ ID NOs: 348, 75), anti-IL23R-VEGFR. In a further embodiment, the fusion protein comprises an additional receptor ECD selected from the following list: SIGLEC10 ECD, SIRPa ECD, BTLA ECD, PD1 ECD, TIM3 ECD.

In some embodiments, the fusion protein comprises VEGFR ECD and a targeting polypeptide that binds and disables a T cell co-inhibitory molecule. In some embodiments, the targeting polypeptide is an antibody. Exemplary embodiments include BTLA-Fc-VEGFR (e.g., SEQ ID NO: 534), PD1-Fc-VEGFR (e.g., SEQ ID NO: 540), TIM3-Fc-VEGFR (e.g., SEQ ID NO: 564), and anti-PDL1-VEGFR (e.g., SEQ ID NOs: 468, 109).

In some embodiments, the fusion protein comprises VEGFR ECD and an antibody that binds an ectonucleotidase. The ectonucleotidase is preferably CD39 or CD73. In a further embodiment, the fusion protein comprises an additional receptor ECD fused to the light chain of the antibody. Exemplary embodiments include anti-CD39-VEGFR-BTLA and anti-CD73-VEGFR-BTLA (e.g., SEQ ID NOs: 427, 422).

In one embodiment, the fusion protein comprises a polypeptide that binds a T cell co-stimulatory molecule and VEGFR ECD. In some embodiments, the fusion protein is a native T cell co-stimulatory molecule ECD fused to VEGFR (either N-costimulatory ECD-Fc-VEGFR ECD-C, or N-VEGFR ECD-Fc-costimulatory ECD-C). In some embodiments, this fusion protein is selected from: 41BBL-Fc-VEGFR (e.g., SEQ ID NO: 632); OX40L-Fc-VEGFR (e.g., SEQ ID NO: 646); ICOSL-Fc-VEGFR (e.g., SEQ ID NO: 642), VEGFR-Fc-41BBL (e.g., SEQ ID NO: 631); VEGFR-Fc-ICOSL (e.g., SEQ ID NO: 641); VEGFR-Fc-OX40L (e.g., SEQ ID NO: 645). In other embodiments, the fusion protein comprises an antibody or other polypeptide that binds a T cell co-stimulatory molecule fused to VEGFR. This antibody or polypeptide is preferably an agonist of the T cell co-stimulatory molecule. In some embodiments, this fusion protein is selected from: anti-OX40-VEGFR (e.g., SEQ ID NOs: 516, 97); anti-41BB-VEGFR (e.g., SEQ ID NOs: 504, 2); anti-ICOS-VEGFR (e.g., SEQ ID NOs: 528, 59).

In various embodiments, the fusion proteins of the invention counteract TGFb in the tumor microenvironment.

In some embodiments, the fusion proteins of the invention comprise a targeting polypeptide that binds TGFb, TGFbR, LAP, or GARP fused to one or more receptor ECDs. These receptor ECDs are preferably selected from the following: PD1 ECD, TIM-3 ECD, VEGFR ECD, BTLA ECD, SIRPa ECD, SIGLEC10 ECD. In some embodiments, the targeting polypeptide that binds TGFb, TGFbR, LAP, or GARP is an antibody. Exemplary embodiments include anti-TGFb-PD1 (e.g., SEQ ID NOs: 398, 133); anti-TGFb-SIRPa (e.g., SEQ ID NOs: 401, 133); anti-TGFb-TIM3 (e.g., SEQ ID NOs: 402, 133); anti-TGFb-SIGLEC10 (e.g., SEQ ID NOs: 400, 133); anti-TGFb-BTLA (e.g., SEQ ID NOs: 393, 133); anti-TGFb-VEGFR (e.g., SEQ ID NOs: 403, 133). In another embodiment, the fusion protein comprises antibody that binds TGFb, TGFbR, LAP, or GARP fused to one receptor ECD on heavy chain and another receptor ECD fused on light chain. Exemplary embodiments include anti-TGFb-SIRPa-BTLA (e.g., SEQ ID NOs: 401, 399); anti-TGFb-BTLA-TIM3 (e.g., SEQ ID NOs: 393, 397); anti-TGFb-PD1-BTLA (e.g., SEQ ID NOs: 398, 399); anti-TGFb-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 402, 395); anti-TGFb-TIM3-BTLA (e.g., SEQ ID NOs: 402, 399); anti-TGFb-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 393, 395); anti-TGFb-SIGLEC10-TIM3 (e.g., SEQ ID NOs: 400, 397); anti-TGFb-BTLA-PD1 (e.g., SEQ ID NOs: 393, 394); anti-TGFb-SIGLEC10-SIRPa (e.g., SEQ ID NOs: 400, 396); anti-TGFb-VEGFR-BTLA (e.g., SEQ ID NOs: 403, 399); anti-TGFb-PD1-TIM3 (e.g., SEQ ID NOs: 398, 397); anti-TGFb-BTLA-SIRPa (e.g., SEQ ID NOs: 393, 396); anti-TGFb-PD1-SIRPa (e.g., SEQ ID NOs: 398, 396); anti-TGFb-SIGLEC10-PD1 (e.g., SEQ ID NOs: 400, 394); anti-TGFb-SIRPa-TIM3 (e.g., SEQ ID NOs: 401, 397); anti-TGFb-SIRPa-PD1 (e.g., SEQ ID NOs: 401, 394); anti-TGFb-TIM3-PD1 (e.g., SEQ ID NOs: 402, 394); anti-TGFb-VEGFR-TIM3 (e.g., SEQ ID NOs: 403, 397); anti-TGFb-VEGFR-PD1 (e.g., SEQ ID NOs: 403, 394); anti-TGFb-TIM3-SIRPa (e.g., SEQ ID NOs: 402, 396); anti-TGFb-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 401, 395); anti-TGFb-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 403, 395); anti-TGFb-PD1-SIGLEC10 (e.g., SEQ ID NOs: 398, 395); anti-TGFb-VEGFR-SIRPa (e.g., SEQ ID NOs: 403, 396); anti-TGFb-SIGLEC10-BTLA (e.g., SEQ ID NOs: 400, 399).

In various embodiments, the fusion proteins of the invention counteract TGFb in the tumor microenvironment. In some embodiments, the fusion proteins comprise a ligand-binding sequence of an extracellular domain of TGFbR (e.g., TGFbRII ECD). In one embodiment, this ligand trap binds TGFb1, TGFb2, and/or TGFb3. In some embodiments, the TGFbR ECD may be a ligand-binding sequence of TGFbRII ECD. In some embodiments, the TGFbR ECD may be a fusion of domains from TGFbRII and TGFbRIII. In some embodiments, the TGFbR ECD may be selected from the following list: SEQ ID NOS: 177; 178; 179; 180

TGFb is known to interfere with phagocytosis and FcR-mediated cross-presentation. In some embodiments, the fusion protein comprises TGFbRII ECD and a polypeptide that inhibits the interaction between CD47 and SIRPa. In one embodiment, this fusion protein is anti-CD47 mAb fused to TGFbRII ECD (anti-CD47-TGFbRII (e.g., SEQ ID NOs: 390, 22)). In another embodiment, this fusion protein comprises SIRPa ECD and TGFbRII ECD. In one embodiment, this fusion protein is SIRPa-Fc-TGFbRII (e.g., SEQ ID NO: 550) or TGFbRII-Fc-SIRPa (e.g., SEQ ID NO: 556).

In other embodiments, the fusion protein comprises TGFbRII ECD, a polypeptide that inhibits the interaction between CD47 and SIRPa, and an additional receptor ECD selected from PD1 ECD, BTLA ECD, TIM-3 ECD, SIGLEC 10 ECD. Exemplary embodiments of this fusion protein include anti-CD47-TGFbRII-PD1 (e.g., SEQ ID NOs: 390, 384), anti-CD47-TGFbRII-BTLA (e.g., SEQ ID NOs: 390, 388) and anti-CD47-TGFbRII-TIM3 (e.g., SEQ ID NOs: 390, 386).

TGFb directly interferes with antibody-dependent cellular cytotoxicity (ADCC) mediated by tumor-targeted antibodies, and cross-presentation. In some embodiments, the fusion protein comprises a tumor-targeted antibody and TGFbRII ECD. In some embodiments, this tumor targeted-antibody binds a tumor growth factor or growth factor receptor. In other embodiments, this tumor targeted antibody binds a tumor cell surface molecule. Exemplary embodiments of this fusion protein include, for example, anti-EGFRvIII-TGFbRII (e.g., SEQ ID NOs: 241, 47), anti-uPAR-TGFbRII (e.g., SEQ ID NOs: 272, 162), anti-PSMA-TGFbRII (e.g., SEQ ID NOs: 279, 121), anti-nectin4-TGFbRII (e.g., SEQ ID NOs: 265, 160).

In a further embodiment, the fusion protein is a tumor-targeted antibody-drug conjugate fused to TGFbRII ECD. For example, the fusion protein may comprise enfortumab vedotin fused to TGFbRII ECD. In a further embodiment, the fusion protein is a bispecific antibody that simultaneously binds a tumor cell and a T cell, fused to TGFbRII ECD. For example, the fusion protein may comprise CD3×EGFRvIII (e.g., AMG596) fused to TGFbRII ECD or CD3×CEA (e.g., cibisatamab) fused to TGFbRII ECD or CD3×HER2 (e.g., GBR1302, M802, RG6194) fused to TGFbRII ECD.

In a further embodiment, the fusion protein comprises a tumor-targeted antibody, TGFbRII fused to the heavy chain, and an additional receptor ECD fused to the light chain of the antibody selected from one of the following: PD1 ECD, BTLA ECD, TIM-3 ECD. Exemplary embodiments of this fusion protein include anti-PSMA-TGFbRII-PD1, anti-PSMA-TGFbRII-BTLA, anti-nectin4-TGFbRII-PD1 (e.g., SEQ ID NOs: 265, 257), or anti-nectin4-TGFbRII-BTLA (e.g., SEQ ID NOs: 265, 262).

In some embodiments, the fusion protein comprises TGFbRII ECD and an antibody that binds and disables a T cell co-inhibitory molecule. Exemplary embodiments of the invention are anti-PVRIG-TGFbRII and anti-TIGIT-TGFbRII (e.g., SEQ ID NOs: 478, 139). In some embodiments, the fusion protein comprises TGFbRII ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and an additional receptor ECD. In one aspect, the TGFbRII ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. The T cell co-inhibitory molecule may be selected from the following: PD1, PDL1, CTLA4, TIGIT, TIM3. In other embodiments, the fusion protein comprises TGFbRII ECD and the ECD of a T cell co-inhibitory molecule, selected from BTLA ECD, TIM-3 ECD. Exemplary embodiments of the invention are anti-PDL1-TGFbRII-BTLA (e.g., SEQ ID NOs: 466, 464), anti-CTLA4-TGFbRII-BTLA (e.g., SEQ ID NOs: 444, 441), anti-PD1-TGFbRII-BTLA (e.g., SEQ ID NOs: 456, 453), and anti-TIGIT-TGFbRII-BTLA (e.g., SEQ ID NOs: 478, 475).

In some embodiments, the fusion protein comprises TGFbRII ECD and an antibody that binds an ectonucleotidase. The ectonucleotidase is preferably CD39 or CD73. In a further embodiment, the fusion protein comprises an additional receptor ECD fused to the light chain of the antibody. Exemplary embodiments include anti-CD39-TGFbRII-BTLA and anti-CD73-TGFbRII-BTLA (e.g., SEQ ID NOs: 425, 422).

In one embodiment, the fusion protein comprises a polypeptide that binds a T cell co-stimulatory molecule and TGFbRII ECD. In some embodiments, the fusion protein is a native T cell co-stimulatory molecule ECD fused to TGFbRII (either N-costimulatory ECD-Fc-TGFbRII ECD-C, or N-TGFbRII ECD-Fc-costimulatory ECD-C). In some embodiments, this fusion protein is selected from: 41BBL-Fc-TGFbRII (e.g., SEQ ID NO: 616); ICOSL-Fc-TGFbRII (e.g., SEQ ID NO: 626); OX40L-Fc-TGFbRII (e.g., SEQ ID NO: 630), TGFbRII-Fc-ICOSL (e.g., SEQ ID NO: 625); TGFbRII-Fc-OX40L (e.g., SEQ ID NO: 629); TGFbRII-Fc-41BBL (e.g., SEQ ID NO: 615). In other embodiments, the fusion protein comprises an antibody or other polypeptide that binds a T cell co-stimulatory molecule fused to TGFbRII. This antibody or polypeptide is preferably an agonist of the T cell co-stimulatory molecule. In some embodiments, this fusion protein is selected from: anti-ICOS-TGFbRII (e.g., SEQ ID NOs: 526, 59); anti-OX40-TGFbRII (e.g., SEQ ID NOs: 514, 97); anti-41BB-TGFbRII (e.g., SEQ ID NOs: 502, 2).

In some embodiments, the fusion protein comprises TGFbRII ECD and a polypeptide that inhibits VEGF/VEGFR signaling. In some embodiments, the fusion protein comprises TGFbRII ECD and anti-VEGFR mAb. In a further embodiment, the fusion protein may additionally comprise a receptor ECD fused to the light chain of the antibody. In some embodiments, the fusion protein is selected from anti-VEGFR-TGFbRII-TIM3 (e.g., SEQ ID NOs: 381, 376); anti-VEGFR-TGFbRII-BTLA (e.g., SEQ ID NOs: 381, 378); anti-VEGFR-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 381, 374); anti-VEGFR-TGFbRII-PD1 (e.g., SEQ ID NOs: 381, 373); anti-VEGFR-TGFbRII-SIRPa (e.g., SEQ ID NOs: 381, 375). In some embodiments, the fusion protein comprises TGFbRII ECD and anti-VEGF mAb. In a further embodiment, the fusion protein may additionally comprise a receptor ECD fused to the light chain of the antibody. In some embodiments, the fusion protein is selected from anti-VEGF-TGFbRII-TIM3 (e.g., SEQ ID NOs: 370, 365); anti-VEGF-TGFbRII-SIRPa (e.g., SEQ ID NOs: 370, 364); anti-VEGF-TGFbRII-PD1 (e.g., SEQ ID NOs: 370, 362); anti-VEGF-TGFbRII-BTLA (e.g., SEQ ID NOs: 370, 367); anti-VEGF-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 370, 363). In other embodiments, the fusion protein comprises TGFbRII ECD and VEGFR ECD. In one embodiment, this fusion protein is TGFbRII-Fc-VEGFR (e.g., SEQ ID NO: 558). In another embodiment, this fusion protein is VEGFR-Fc-TGFbRII (e.g., SEQ ID NO: 569).

TGFb is a major determinant of TH17 differentiation and function, along with IL-17/IL-17R, IL-6/IL-6R, IL-23/IL-23R. In some embodiments, the fusion protein comprises TGFbRII ECD and an antibody that binds and disables IL-17/IL-17R, IL-23/IL-23R, or IL-6/IL-6R. In some embodiments, the fusion protein is selected from the following: anti-IL17-TGFbRII, anti-IL17R-TGFbRII (e.g., SEQ ID NOs: 334, 63), anti-IL23-TGFbRII (e.g., SEQ ID NOs: 346, 75), anti-IL23R-TGFbRII. In a further embodiment, the fusion protein comprises an additional receptor ECD selected from the following list: SIGLEC10 ECD, SIRPa ECD, BTLA ECD, PD1 ECD, TIM3 ECD.

In some embodiments, the fusion protein comprises TGFbRII ECD and an IL-15R binding fragment of IL-15, or an IL-12R binding fragment of IL-12. Exemplary embodiments include IL15-Fc-TGFbRII (e.g., SEQ ID NO: 590), TGFbRII-Fc-IL15 (e.g., SEQ ID NO: 589), IL12-Fc-TGFbRII (e.g., SEQ ID NO: 588) and TGFbRII-Fc-IL12 (e.g., SEQ ID NO: 587).

In various embodiments, the fusion proteins of the invention counteract PD1/PDL1 in the tumor microenvironment.

In various embodiments, the fusion protein comprises a ligand-binding sequence of an extracellular domain of PD1 (PD1 ECD). In some embodiments, the fusion protein comprises an antibody and PD1 ECD. In one embodiment, the PD1 ECD is fused to the heavy chain of the antibody. In another embodiment, the PD1 ECD is fused to the light chain of the antibody. In a preferred aspect, PD1 ECD is fused to C terminus of antibody heavy chain or light chain. In another aspect, PD1 ECD is fused to N terminus of antibody heavy chain or light chain.

In some embodiments, the fusion protein comprises PD1 ECD and a polypeptide that inhibits the interaction between CD47 and SIRPa. In one embodiment, this fusion protein is anti-CD47 mAb fused to PD1 ECD (e.g., anti-CD47-PD1 (e.g., SEQ ID NOs: 387, 22)). In another embodiment, this fusion protein comprises SIRPa ECD and PD1 ECD. In one embodiment, this fusion protein is SIRPa-Fc-PD1 (e.g., SEQ ID NO: 548) or PD1-Fc-SIRPa (e.g., SEQ ID NO: 537).

In a further aspect, the fusion protein comprises PD1 ECD, a polypeptide that inhibits the interaction between CD47 and SIRPa, and another polypeptide that inhibits a T cell co-inhibitory molecule. In some embodiments, this fusion protein comprises anti-CD47 mAb with PD1 ECD fused to the heavy chain or light chain; and the ECD of an immuno-inhibitory molecule fused to the other chain. In a preferred embodiment, the immuno-inhibitory molecule suppresses immune cells via ITIM/ITSMs. In a particular embodiment, this fusion protein is anti-CD47-PD1-TIM3 (e.g., SEQ ID NOs: 387, 386); anti-CD47-PD1-BTLA (e.g., SEQ ID NOs: 387, 388); anti-CD47-PD1-SIGLEC10 (e.g., SEQ ID NOs: 387, 385).

In another aspect, the fusion protein comprises PD1 ECD, anti-CD47 mAb, and VEGFR ECD. In some embodiments, VEGFR ECD is fused to heavy chain of anti-CD47 mAb and PD1 ECD is fused to light chain of anti-CD47 mAb. In one embodiment, this fusion protein is anti-CD47-VEGFR-PD1 (e.g., SEQ ID NOs: 392, 384).

In another aspect, the fusion protein comprises PD1 ECD, SIRPa ECD, and an targeting polypeptide that is an antibody with a heavy chain and light chain. In one aspect, the PD1 ECD is fused to the heavy chain of the antibody and the SIRPa ECD is fused to the light chain of the antibody. Exemplary embodiments include anti-CTLA4-PD1-SIRPa (e.g., SEQ ID NOs: 440, 438), anti-TIM3-PD1-SIRPa (e.g., SEQ ID NOs: 486, 484), anti-PDL1-PD1-SIRPa, anti-EGFR-PD1-SIRPa (e.g., SEQ ID NOs: 225, 223), anti-HER2-PD1-SIRPa (e.g., SEQ ID NOs: 249, 247), anti-EGFRvIII-PD1-SIRPa (e.g., SEQ ID NOs: 237, 235), anti-uPAR-PD1-SIRPa, anti-PSMA-PD1-SIRPa, anti-TGFb-PD1-SIRPa (e.g., SEQ ID NOs: 398, 396), anti-TGFbR-PD1-SIRPa, and anti-GARP-PD1-SIRPa, anti-VEGF-PD1-SIRPa (e.g., SEQ ID NOs: 366, 364), and anti-VEGFR-PD1-SIRPa (e.g., SEQ ID NOs: 377, 375).

In some embodiments, the fusion protein comprises PD1 ECD and a polypeptide that inhibits a T cell co-inhibitory molecule. In specific embodiments, the fusion protein comprises PD1 ECD and an antibody that binds and disables a T cell co-inhibitory molecule. Exemplary embodiments include anti-CTLA4-PD1 (e.g., SEQ ID NOs: 440, 28); anti-PD1-PD1 (e.g., SEQ ID NOs: 452, 101); anti-TIGIT-PD1 (e.g., SEQ ID NOs: 474, 139); anti-TIM3-PD1 (e.g., SEQ ID NOs: 486, 141). Additional exemplary embodiments are anti-PDL1 mAb fused to PD1 ECD where the anti-PDL1 mAb is atezolizumab (SEQ ID NOs: 108, 109); avelumab (SEQ ID NOs: 110, 111); durvalumab (SEQ ID NOs: 112, 113). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIGLEC10 ECD, SIRPa ECD, TGFbRII ECD, TIM3 ECD, BTLA ECD, VEGFR ECD.

In some embodiments, the fusion protein comprises an antibody that binds a T cell co-stimulatory molecule fused to PD1. This antibody is preferably an agonist of the T cell co-stimulatory molecule. In some embodiments, this fusion protein is selected from: anti-ICOS-PD1 (e.g., SEQ ID NOs: 522, 59); anti-41BB-PD1 (e.g., SEQ ID NOs: 498, 2); anti-OX40-PD1 (e.g., SEQ ID NOs: 510, 97). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIGLEC10 ECD, SIRPa ECD, TGFbRII ECD, TIM3 ECD, BTLA ECD, VEGFR ECD.

In one embodiment, the fusion protein comprises PD1 ECD and a polypeptide that binds either CD39 or CD73. In some embodiments, the fusion protein is an antibody that binds CD39 or CD73 fused to PD1 ECD; for example: anti-CD39-PD1 (e.g., SEQ ID NOs: 429, 18) or anti-CD73-PD1 (e.g., SEQ ID NOs: 421, 24). In some embodiments, the fusion protein comprises an additional receptor ECD fused to the antibody selected from [ECD]. In some embodiments, the fusion protein is selected from: anti-CD73-PD1-SIRPa (e.g., SEQ ID NOs: 421, 419); anti-CD73-PD1-BTLA (e.g., SEQ ID NOs: 421, 422); anti-CD73-PD1-TIM3 (e.g., SEQ ID NOs: 421, 420); anti-CD73-PD1-SIGLEC10 (e.g., SEQ ID NOs: 421, 418).

In some embodiments, the fusion protein comprises a tumor-targeted antibody and PD1 ECD. In some embodiments, this tumor targeted-antibody binds a tumor growth factor, growth factor receptor, or tumor cell surface molecule. In some embodiments, this fusion protein is selected from: anti-EGFR-PD1 (e.g., SEQ ID NOs: 225, 43), anti-HER2-PD1 (e.g., SEQ ID NOs: 249, 55), anti-EGFRvIII-PD1 (e.g., SEQ ID NOs: 237, 47), anti-uPAR-PD1 (e.g., SEQ ID NOs: 269, 162), anti-PSMA-PD1 (e.g., SEQ ID NOs: 276, 121), anti-nectin4-PD1 (e.g., SEQ ID NOs: 261, 160). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIGLEC10 ECD, SIRPa ECD, TGFbRII ECD, TIM3 ECD, BTLA ECD, VEGFR ECD.

In some embodiments, the fusion protein comprises PD1 ECD and an antibody that binds and disables IL-17/IL-17R, IL-23/IL-23R, or IL-6/IL-6R. In some embodiments, the fusion protein is selected from: anti-IL17-PD1, anti-IL17R-PD1 (e.g., SEQ ID NOs: 330, 63), anti-IL23-PD1 (e.g., SEQ ID NOs: 342, 75), anti-IL23R-PD1, anti-IL6-PD1, anti-IL6R-PD1 (e.g., SEQ ID NOs: 318, 79). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIGLEC10 ECD, SIRPa ECD, TGFbRII ECD, TIM3 ECD, BTLA ECD, VEGFR ECD.

In some embodiments, the fusion protein comprises PD1 ECD and an antibody that binds TGFb, TGFbR, or GARP. Exemplary embodiments of this fusion protein include anti-TGFb-PD1 (e.g., SEQ ID NOs: 398, 133), anti-TGFbR-PD1, and anti-GARP-PD1 (e.g., SEQ ID NOs: 411, 49). In some embodiments, the fusion protein further comprises an additional receptor ECD. Exemplary embodiments of this fusion protein include anti-TGFb-PD1-SIRPa (e.g., SEQ ID NOs: 398, 396); anti-TGFb-PD1-BTLA (e.g., SEQ ID NOs: 398, 399); anti-TGFb-PD1-SIGLEC10 (e.g., SEQ ID NOs: 398, 395); anti-TGFb-PD1-TIM3 (e.g., SEQ ID NOs: 398, 397).

In some embodiments, the fusion protein comprises PD1 ECD and IL-15. In some embodiments, the fusion protein is IL15-Fc-PD1 (e.g., SEQ ID NO: 578), PD1-Fc-IL15 (e.g., SEQ ID NO: 577), IL12-Fc-PD1 (e.g., SEQ ID NO: 576) or PD1-Fc-IL12 (e.g., SEQ ID NO: 575).

In some embodiments, the fusion proteins of the invention comprise a targeting polypeptide that binds PD1 or PDL1 fused to one or more receptor ECDs. These receptor ECDs are preferably selected from: TIM3 ECD, BTLA ECD, VEGFR ECD, TGFbRII ECD, SIRPa ECD, SIGLEC10 ECD. In some embodiments, the targeting polypeptide that binds PD1 or PDL1 is an antibody. Exemplary embodiments include anti-PD1-SIRPa (e.g., SEQ ID NOs: 455, 101); anti-PD1-VEGFR (e.g., SEQ ID NOs: 458, 101); anti-PD1-BTLA (e.g., SEQ ID NOs: 447, 101); anti-PD1-PD1 (e.g., SEQ ID NOs: 452, 101); anti-PD1-TIM3 (e.g., SEQ ID NOs: 457, 101); anti-PD1-SIGLEC10 (e.g., SEQ ID NOs: 454, 101); anti-PD1-TGFbR (e.g., SEQ ID NOs: 456, 101). In another embodiment, the fusion protein comprises antibody that binds PD1 or PDL1 fused to one receptor ECD on heavy chain and another receptor ECD fused on light chain.

In various embodiments, the fusion proteins of the invention counteract TIM3/CEACAM in the tumor microenvironment.

In various embodiments, the fusion protein comprises a ligand-binding sequence of an extracellular domain of TIM-3 (TIM3 ECD). In some embodiments, the fusion protein comprises an antibody and TIM3 ECD. In one embodiment, the TIM3 ECD is fused to the heavy chain of the antibody. In another embodiment, the TIM3 ECD is fused to the light chain of the antibody. In a preferred aspect, TIM3 ECD is fused to C terminus of antibody heavy chain or light chain. In another aspect, TIM3 ECD is fused to N terminus of antibody heavy chain or light chain.

In some embodiments, the fusion protein comprises TIM3 ECD and a polypeptide that inhibits the interaction between CD47 and SIRPa. In one embodiment, this fusion protein is anti-CD47 mAb fused to TIM3 ECD (e.g., anti-CD47-TIM3 (e.g., SEQ ID NOs: 391, 22)). In another embodiment, this fusion protein comprises SIRPa ECD and TIM3 ECD. In one embodiment, this fusion protein is SIRPa-Fc-TIM3 (e.g., SEQ ID NO: 551) or TIM3-Fc-SIRPa (e.g., SEQ ID NO: 562).

In a further aspect, the fusion protein comprises TIM3 ECD, a polypeptide that inhibits the interaction between CD47 and SIRPa, and another polypeptide that inhibits a T cell co-inhibitory molecule. In some embodiments, this fusion protein comprises anti-CD47 mAb with TIM3 ECD fused to the heavy chain or light chain; and the ECD of an immuno-inhibitory molecule fused to the other chain. In a preferred embodiment, the immuno-inhibitory molecule suppresses immune cells via ITIM/ITSMs. In a particular embodiment, this fusion protein is anti-CD47-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 391, 385); anti-CD47-TIM3-PD1 (e.g., SEQ ID NOs: 391, 384); anti-CD47-TIM3-BTLA (e.g., SEQ ID NOs: 391, 388).

In another aspect, the fusion protein comprises TIM3 ECD, anti-CD47 mAb, and VEGFR ECD. In some embodiments, VEGFR ECD is fused to heavy chain of anti-CD47 mAb and TIM3 ECD is fused to light chain of anti-CD47 mAb. In one embodiment, this fusion protein is anti-CD47-VEGFR-TIM3 (e.g., SEQ ID NOs: 392, 386).

In another aspect, the fusion protein comprises TIM3 ECD, SIRPa ECD, and a targeting polypeptide that is an antibody with a heavy chain and light chain. In one aspect, the TIM3 ECD is fused to the heavy chain of the antibody and the SIRPa ECD is fused to the light chain of the antibody. Exemplary embodiments include anti-CTLA4-TIM3-SIRPa (e.g., SEQ ID NOs: 445, 438), anti-PD1-TIM3-SIRPa (e.g., SEQ ID NOs: 457, 450), anti-PDL1-TIM3-SIRPa (e.g., SEQ ID NOs: 467, 461), anti-EGFR-TIM3-SIRPa (e.g., SEQ ID NOs: 230, 223), anti-HER2-TIM3-SIRPa (e.g., SEQ ID NOs: 254, 247), anti-EGFRvIII-TIM3-SIRPa (e.g., SEQ ID NOs: 242, 235), anti-uPAR-TIM3-SIRPa, anti-PSMA-TIM3-SIRPa, anti-TGFb-TIM3-SIRPa (e.g., SEQ ID NOs: 402, 396), anti-TGFbR-TIM3-SIRPa, and anti-GARP-TIM3-SIRPa, anti-VEGF-TIM3-SIRPa (e.g., SEQ ID NOs: 371, 364), and anti-VEGFR-TIM3-SIRPa (e.g., SEQ ID NOs: 382, 375).

In some embodiments, the fusion protein comprises TIM3 ECD and a polypeptide that inhibits a T cell co-inhibitory molecule. In specific embodiments, the fusion protein comprises TIM3 ECD and an antibody that binds and disables a T cell co-inhibitory molecule. Exemplary embodiments include anti-CTLA4-TIM3 (e.g., SEQ ID NOs: 445, 28); anti-TIM3-TIM3 (e.g., SEQ ID NOs: 491, 141); anti-PD1-TIM3 (e.g., SEQ ID NOs: 457, 101); anti-TIGIT-TIM3 (e.g., SEQ ID NOs: 479, 139); anti-PDL1-TIM3 (e.g., SEQ ID NOs: 467, 109). Additional exemplary embodiments are anti-PDL1 mAb fused to TIM3 ECD where the anti-PDL1 mAb is atezolizumab (SEQ ID NOs: 108, 109); avelumab (SEQ ID NOs: 110, 111); durvalumab (SEQ ID NOs: 112, 113). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIGLEC10 ECD, SIRPa ECD, TGFbRII ECD, PD1 ECD, BTLA ECD, VEGFR ECD.

In some embodiments, the fusion protein comprises an antibody that binds a T cell co-stimulatory molecule fused to TIM3. This antibody is preferably an agonist of the T cell co-stimulatory molecule. In some embodiments, this fusion protein is selected from: anti-41BB-TIM3 (e.g., SEQ ID NOs: 503, 2); anti-OX40-TIM3 (e.g., SEQ ID NOs: 515, 97); anti-ICOS-TIM3 (e.g., SEQ ID NOs: 527, 59). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIGLEC10 ECD, SIRPa ECD, TGFbRII ECD, PD1 ECD, BTLA ECD, VEGFR ECD.

In one embodiment, the fusion protein comprises TIM3 ECD and a polypeptide that binds either CD39 or CD73. In some embodiments, the fusion protein is an antibody that binds CD39 or CD73 fused to TIM3 ECD; for example: anti-CD39-TIM3 (e.g., SEQ ID NOs: 433, 18) or anti-CD73-TIM3 (e.g., SEQ ID NOs: 426, 24). In some embodiments, the fusion protein comprises an additional receptor ECD fused to the antibody selected from [ECD]. In some embodiments, the fusion protein is selected from the following: anti-CD73-TIM3-SIRPa (e.g., SEQ ID NOs: 426, 419); anti-CD73-TIM3-PD1 (e.g., SEQ ID NOs: 426, 417); anti-CD73-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 426, 418); anti-CD73-TIM3-BTLA (e.g., SEQ ID NOs: 426, 422).

In some embodiments, the fusion protein comprises a tumor-targeted antibody and TIM3 ECD. In some embodiments, this tumor targeted-antibody binds a tumor growth factor, growth factor receptor, or tumor cell surface molecule. In some embodiments, this fusion protein is selected from the following: anti-EGFR-TIM3 (e.g., SEQ ID NOs: 230, 43), anti-HER2-TIM3 (e.g., SEQ ID NOs: 254, 55), anti-EGFRvIII-TIM3 (e.g., SEQ ID NOs: 242, 47), anti-uPAR-TIM3 (e.g., SEQ ID NOs: 273, 162), anti-PSMA-TIM3 (e.g., SEQ ID NOs: 280, 121), anti-nectin4-TIM3 (e.g., SEQ ID NOs: 266, 160). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIGLEC10 ECD, SIRPa ECD, TGFbRII ECD, PD1 ECD, BTLA ECD, VEGFR ECD.

In some embodiments, the fusion protein comprises TIM3 ECD and an antibody that binds and disables IL-17/IL-17R, IL-23/IL-23R, or IL-6/IL-6R. In some embodiments, the fusion protein is selected from the following: anti-IL17-TIM3, anti-IL17R-TIM3 (e.g., SEQ ID NOs: 335, 63), anti-IL23-TIM3 (e.g., SEQ ID NOs: 347, 75), anti-IL23R-TIM3, anti-IL6-TIM3, anti-IL6R-TIM3 (e.g., SEQ ID NOs: 323, 79). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIGLEC10 ECD, SIRPa ECD, TGFbRII ECD, PD1 ECD, BTLA ECD, VEGFR ECD.

In some embodiments, the fusion protein comprises TIM3 ECD and an antibody that binds TGFb, TGFbR, or GARP. Exemplary embodiments of this fusion protein include anti-TGFb-TIM3 (e.g., SEQ ID NOs: 402, 133), anti-TGFbR-TIM3, and anti-GARP-TIM3 (e.g., SEQ ID NOs: 414, 49). In some embodiments, the fusion protein further comprises an additional receptor ECD. Exemplary embodiments of this fusion protein include anti-TGFb-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 402, 395); anti-TGFb-TIM3-BTLA (e.g., SEQ ID NOs: 402, 399); anti-TGFb-TIM3-PD1 (e.g., SEQ ID NOs: 402, 394); anti-TGFb-TIM3-SIRPa (e.g., SEQ ID NOs: 402, 396).

In some embodiments, the fusion protein comprises TIM3 ECD and IL-15. In some embodiments, the fusion protein is IL15-Fc-TIM3 (e.g., SEQ ID NO: 594), TIM3-Fc-IL15 (e.g., SEQ ID NO: 593), IL12-Fc-TIM3 (e.g., SEQ ID NO: 592) or TIM3-Fc-IL12 (e.g., SEQ ID NO: 591).

In some embodiments, the fusion proteins of the invention comprise a targeting polypeptide that binds TIM3 or CEACAM fused to one or more receptor ECDs. These receptor ECDs are preferably selected from the following: PD1 ECD, BTLA ECD, VEGFR ECD, TGFbRII ECD, SIRPa ECD, SIGLEC10 ECD. In some embodiments, the targeting polypeptide that binds TIM3 or CEACAM is an antibody. Exemplary embodiments include anti-TIM3-SIRPa (e.g., SEQ ID NOs: 489, 141); anti-TIM3-TGFbR (e.g., SEQ ID NOs: 490, 141); anti-TIM3-VEGFR (e.g., SEQ ID NOs: 492, 141); anti-TIM3-TIM3 (e.g., SEQ ID NOs: 491, 141); anti-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 488, 141); anti-TIM3-BTLA (e.g., SEQ ID NOs: 481, 141); anti-TIM3-PD1 (e.g., SEQ ID NOs: 486, 141). In another embodiment, the fusion protein comprises antibody that binds TIM3 or CEACAM fused to one receptor ECD on heavy chain and another receptor ECD fused on light chain.

In various embodiments, the fusion proteins of the invention counteract BTLA/HVEM in the tumor microenvironment.

In various embodiments, the fusion protein comprises a ligand-binding sequence of an extracellular domain of B- and T-lymphocyte attenuator (BTLA ECD). In some embodiments, the fusion protein comprises an antibody and BTLA ECD. In one embodiment, the BTLA ECD is fused to the heavy chain of the antibody. In another embodiment, the BTLA ECD is fused to the light chain of the antibody. In a preferred aspect, BTLA ECD is fused to C terminus of antibody heavy chain or light chain. In another aspect, BTLA ECD is fused to N terminus of antibody heavy chain or light chain.

In some embodiments, the fusion protein comprises BTLA ECD and a polypeptide that inhibits the interaction between CD47 and SIRPa. In one embodiment, this fusion protein is anti-CD47 mAb fused to BTLA ECD (e.g., anti-CD47-BTLA (e.g., SEQ ID NOs: 383, 22)). In another embodiment, this fusion protein comprises SIRPa ECD and BTLA ECD. In one embodiment, this fusion protein is SIRPa-Fc-BTLA (e.g., SEQ ID NO: 547) or BTLA-Fc-SIRPa (e.g., SEQ ID NO: 531).

In a further aspect, the fusion protein comprises BTLA ECD, a polypeptide that inhibits the interaction between CD47 and SIRPa, and another polypeptide that inhibits a T cell co-inhibitory molecule. In some embodiments, this fusion protein comprises anti-CD47 mAb with BTLA ECD fused to the heavy chain or light chain; and the ECD of an immuno-inhibitory molecule fused to the other chain. In a preferred embodiment, the immuno-inhibitory molecule suppresses immune cells via ITIM/ITSMs. In a particular embodiment, this fusion protein is anti-CD47-BTLA-TIM3 (e.g., SEQ ID NOs: 383, 386); anti-CD47-BTLA-PD1 (e.g., SEQ ID NOs: 383, 384); anti-CD47-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 383, 385).

In another aspect, the fusion protein comprises BTLA ECD, anti-CD47 mAb, and VEGFR ECD. In some embodiments, VEGFR ECD is fused to heavy chain of anti-CD47 mAb and BTLA ECD is fused to light chain of anti-CD47 mAb. In one embodiment, this fusion protein is anti-CD47-VEGFR-BTLA (e.g., SEQ ID NOs: 392, 388)

In another aspect, the fusion protein comprises BTLA ECD, SIRPa ECD, and an targeting polypeptide that is an antibody with a heavy chain and light chain. In one aspect, the BTLA ECD is fused to the heavy chain of the antibody and the SIRPa ECD is fused to the light chain of the antibody. Exemplary embodiments include anti-CTLA4-BTLA-SIRPa (e.g., SEQ ID NOs: 435, 438), anti-PD1-BTLA-SIRPa (e.g., SEQ ID NOs: 447, 450), anti-PDL1-BTLA-SIRPa (e.g., SEQ ID NOs: 459, 461), anti-EGFR-BTLA-SIRPa (e.g., SEQ ID NOs: 220, 223), anti-HER2-BTLA-SIRPa (e.g., SEQ ID NOs: 244, 247), anti-EGFRvIII-BTLA-SIRPa (e.g., SEQ ID NOs: 232, 235), anti-uPAR-BTLA-SIRPa, anti-PSMA-BTLA-SIRPa, anti-TGFb-BTLA-SIRPa (e.g., SEQ ID NOs: 393, 396), anti-TGFbR-BTLA-SIRPa, and anti-GARP-BTLA-SIRPa, anti-VEGF-BTLA-SIRPa (e.g., SEQ ID NOs: 361, 364), and anti-VEGFR-BTLA-SIRPa (e.g., SEQ ID NOs: 372, 375).

In some embodiments, the fusion protein comprises BTLA ECD and a polypeptide that inhibits a T cell co-inhibitory molecule. In specific embodiments, the fusion protein comprises BTLA ECD and an antibody that binds and disables a T cell co-inhibitory molecule. Exemplary embodiments include anti-PD1-BTLA (e.g., SEQ ID NOs: 447, 101); anti-PDL1-BTLA (e.g., SEQ ID NOs: 459, 109); anti-TIGIT-BTLA (e.g., SEQ ID NOs: 469, 139); anti-CTLA4-BTLA (e.g., SEQ ID NOs: 435, 28); anti-TIM3-BTLA (e.g., SEQ ID NOs: 481, 141). Additional exemplary embodiments are anti-PDL1 mAb fused to BTLA ECD where the anti-PDL1 mAb is atezolizumab (SEQ ID NOs: 108, 109); avelumab (SEQ ID NOs: 110, 111); durvalumab (SEQ ID NOs: 112, 113). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIGLEC10 ECD, SIRPa ECD, TGFbRII ECD, PD1 ECD, TIM3 ECD, VEGFR ECD.

In some embodiments, the fusion protein comprises an antibody that binds a T cell co-stimulatory molecule fused to BTLA. This antibody is preferably an agonist of the T cell co-stimulatory molecule. In some embodiments, this fusion protein is selected from: anti-41BB-BTLA (e.g., SEQ ID NOs: 493, 2); anti-ICOS-BTLA (e.g., SEQ ID NOs: 517, 59); anti-OX40-BTLA (e.g., SEQ ID NOs: 505, 97). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIGLEC10 ECD, SIRPa ECD, TGFbRII ECD, PD1 ECD, TIM3 ECD, VEGFR ECD.

In one embodiment, the fusion protein comprises BTLA ECD and a polypeptide that binds either CD39 or CD73. In some embodiments, the fusion protein is an antibody that binds CD39 or CD73 fused to BTLA ECD; for example: anti-CD39-BTLA (e.g., SEQ ID NOs: 428, 18) or anti-CD73-BTLA (e.g., SEQ ID NOs: 416, 24). In some embodiments, the fusion protein comprises an additional receptor ECD fused to the antibody selected from [ECD]. In some embodiments, the fusion protein is selected from the following: anti-CD73-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 416, 418); anti-CD73-BTLA-SIRPa (e.g., SEQ ID NOs: 416, 419); anti-CD73-BTLA-TIM3 (e.g., SEQ ID NOs: 416, 420); anti-CD73-BTLA-PD1 (e.g., SEQ ID NOs: 416, 417).

In some embodiments, the fusion protein comprises a tumor-targeted antibody and BTLA ECD. In some embodiments, this tumor targeted-antibody binds a tumor growth factor, growth factor receptor, or tumor cell surface molecule. In some embodiments, this fusion protein is selected from the following: anti-EGFR-BTLA (e.g., SEQ ID NOs: 220, 43), anti-HER2-BTLA (e.g., SEQ ID NOs: 244, 55), anti-EGFRvIII-BTLA (e.g., SEQ ID NOs: 232, 47), anti-uPAR-BTLA (e.g., SEQ ID NOs: 268, 162), anti-PSMA-BTLA (e.g., SEQ ID NOs: 275, 121), anti-nectin4-BTLA (e.g., SEQ ID NOs: 256, 160). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIGLEC10 ECD, SIRPa ECD, TGFbRII ECD, PD1 ECD, TIM3 ECD, VEGFR ECD.

In some embodiments, the fusion protein comprises BTLA ECD and an antibody that binds and disables IL-17/IL-17R, IL-23/IL-23R, or IL-6/IL-6R. In some embodiments, the fusion protein is selected from the following: anti-IL17-BTLA, anti-IL17R-BTLA (e.g., SEQ ID NOs: 325, 63), anti-IL23-BTLA (e.g., SEQ ID NOs: 337, 75), anti-IL23R-BTLA, anti-IL6-BTLA, anti-IL6R-BTLA (e.g., SEQ ID NOs: 313, 79). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIGLEC10 ECD, SIRPa ECD, TGFbRII ECD, PD1 ECD, TIM3 ECD, VEGFR ECD.

In some embodiments, the fusion protein comprises BTLA ECD and an antibody that binds TGFb, TGFbR, or GARP. Exemplary embodiments of this fusion protein include anti-TGFb-BTLA (e.g., SEQ ID NOs: 393, 133), anti-TGFbR-BTLA, and anti-GARP-BTLA (e.g., SEQ ID NOs: 410, 49). In some embodiments, the fusion protein further comprises an additional receptor ECD. Exemplary embodiments of this fusion protein include anti-TGFb-BTLA-TIM3 (e.g., SEQ ID NOs: 393, 397); anti-TGFb-BTLA-PD1 (e.g., SEQ ID NOs: 393, 394); anti-TGFb-BTLA-SIRPa (e.g., SEQ ID NOs: 393, 396); anti-TGFb-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 393, 395).

In some embodiments, the fusion protein comprises BTLA ECD and IL-15. In some embodiments, the fusion protein is IL15-Fc-BTLA (e.g., SEQ ID NO: 574), BTLA-Fc-IL15 (e.g., SEQ ID NO: 573), IL12-Fc-BTLA (e.g., SEQ ID NO: 572) or BTLA-Fc-IL12 (e.g., SEQ ID NO: 571).

In some embodiments, the fusion proteins of the invention comprise a targeting polypeptide that binds BTLA or HVEM fused to one or more receptor ECDs. These receptor ECDs are preferably selected from the following: PD1 ECD, TIM-3 ECD, VEGFR ECD, TGFbRII ECD, SIRPa ECD, SIGLEC10 ECD. In some embodiments, the targeting polypeptide that binds BTLA or HVEM is an antibody. In another embodiment, the fusion protein comprises antibody that binds BTLA or HVEM fused to one receptor ECD on heavy chain and another receptor ECD fused on light chain.

In various embodiments, the fusion proteins of the invention counteract SIRPa/CD47 in the tumor microenvironment.

In various embodiments, the fusion protein comprises a ligand-binding sequence of an extracellular domain of SIRPa (SIRPa ECD). In some embodiments, the fusion protein comprises an antibody and SIRPa ECD. In one embodiment, the SIRPa ECD is fused to the heavy chain of the antibody. In another embodiment, the SIRPa ECD is fused to the light chain of the antibody. In a preferred aspect, SIRPa ECD is fused to C terminus of antibody heavy chain or light chain. In another aspect, SIRPa ECD is fused to N terminus of antibody heavy chain or light chain.

In some embodiments, the fusion protein comprises SIRPa ECD and a polypeptide that inhibits a T cell co-inhibitory molecule. In specific embodiments, the fusion protein comprises SIRPa ECD and an antibody that binds and disables a T cell co-inhibitory molecule. Exemplary embodiments include anti-PD1-SIRPa (e.g., SEQ ID NOs: 455, 101); anti-TIM3-SIRPa (e.g., SEQ ID NOs: 489, 141); anti-CTLA4-SIRPa (e.g., SEQ ID NOs: 443, 28); anti-TIGIT-SIRPa (e.g., SEQ ID NOs: 477, 139); anti-PDL1-SIRPa (e.g., SEQ ID NOs: 465, 109). Additional exemplary embodiments are anti-PDL1 mAb fused to SIRPa ECD where the anti-PDL1 mAb is atezolizumab (SEQ ID NOs: 108, 109); avelumab (SEQ ID NOs: 110, 111); durvalumab (SEQ ID NOs: 112, 113). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIGLEC10 ECD, PD1 ECD, TGFbRII ECD, TIM3 ECD, BTLA ECD, VEGFR ECD.

In some embodiments, the fusion protein comprises an antibody that binds a T cell co-stimulatory molecule fused to SIRPa. This antibody is preferably an agonist of the T cell co-stimulatory molecule. In some embodiments, this fusion protein is selected from: anti-ICOS-SIRPa (e.g., SEQ ID NOs: 525, 59); anti-OX40-SIRPa (e.g., SEQ ID NOs: 513, 97); anti-41BB-SIRPa (e.g., SEQ ID NOs: 501, 2). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIGLEC10 ECD, PD1 ECD, TGFbRII ECD, TIM3 ECD, BTLA ECD, VEGFR ECD.

In one embodiment, the fusion protein comprises SIRPa ECD and a polypeptide that binds either CD39 or CD73. In some embodiments, the fusion protein is an antibody that binds CD39 or CD73 fused to SIRPa ECD; for example: anti-CD39-SIRPa (e.g., SEQ ID NOs: 431, 18) or anti-CD73-SIRPa (e.g., SEQ ID NOs: 424, 24). In some embodiments, the fusion protein comprises an additional receptor ECD fused to the antibody selected from [ECD]. In some embodiments, the fusion protein is selected from the following: anti-CD73-SIRPa-BTLA (e.g., SEQ ID NOs: 424, 422); anti-CD73-SIRPa-PD1 (e.g., SEQ ID NOs: 424, 417); anti-CD73-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 424, 418); anti-CD73-SIRPa-TIM3 (e.g., SEQ ID NOs: 424, 420).

In some embodiments, the fusion protein comprises a tumor-targeted antibody and SIRPa ECD. In some embodiments, this tumor targeted-antibody binds a tumor growth factor, growth factor receptor, or tumor cell surface molecule. In some embodiments, this fusion protein is selected from the following: anti-EGFR-SIRPa (e.g., SEQ ID NOs: 228, 43), anti-HER2-SIRPa (e.g., SEQ ID NOs: 252, 55), anti-EGFRvIII-SIRPa (e.g., SEQ ID NOs: 240, 47), anti-uPAR-SIRPa (e.g., SEQ ID NOs: 271, 162), anti-PSMA-SIRPa (e.g., SEQ ID NOs: 278, 121), anti-nectin4-SIRPa (e.g., SEQ ID NOs: 264, 160). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIGLEC10 ECD, PD1 ECD, TGFbRII ECD, TIM3 ECD, BTLA ECD, VEGFR ECD.

In some embodiments, the fusion protein comprises SIRPa ECD and an antibody that binds and disables IL-17/IL-17R, IL-23/IL-23R, or IL-6/IL-6R. In some embodiments, the fusion protein is selected from the following: anti-IL17-SIRPa, anti-IL17R-SIRPa (e.g., SEQ ID NOs: 333, 63), anti-IL23-SIRPa (e.g., SEQ ID NOs: 345, 75), anti-IL23R-SIRPa, anti-IL6-SIRPa, anti-IL6R-SIRPa (e.g., SEQ ID NOs: 321, 79). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIGLEC10 ECD, PD1 ECD, TGFbRII ECD, TIM3 ECD, BTLA ECD, VEGFR ECD.

In some embodiments, the fusion protein comprises SIRPa ECD and an antibody that binds TGFb, TGFbR, or GARP. Exemplary embodiments of this fusion protein include anti-TGFb-SIRPa (e.g., SEQ ID NOs: 401, 133), anti-TGFbR-SIRPa, and anti-GARP-SIRPa (e.g., SEQ ID NOs: 413, 49). In some embodiments, the fusion protein further comprises an additional receptor ECD. Exemplary embodiments of this fusion protein include anti-TGFb-SIRPa-BTLA (e.g., SEQ ID NOs: 401, 399); anti-TGFb-SIRPa-TIM3 (e.g., SEQ ID NOs: 401, 397); anti-TGFb-SIRPa-PD1 (e.g., SEQ ID NOs: 401, 394); anti-TGFb-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 401, 395).

In some embodiments, the fusion protein comprises SIRPa ECD and IL-15. In some embodiments, the fusion protein is IL15-Fc-SIRPa (e.g., SEQ ID NO: 586), SIRPa-Fc-IL15 (e.g., SEQ ID NO: 585), IL12-Fc-SIRPa (e.g., SEQ ID NO: 584) or SIRPa-Fc-IL12 (e.g., SEQ ID NO: 583).

In some embodiments, the fusion proteins of the invention comprise a targeting polypeptide that binds SIRPa or CD47 fused to one or more receptor ECDs. These receptor ECDs are preferably selected from the following: TIM3 ECD, BTLA ECD, VEGFR ECD, TGFbRII ECD, PD1 ECD, SIGLEC10 ECD. In some embodiments, the targeting polypeptide that binds SIRPa or CD47 is an antibody. Exemplary embodiments include anti-CD47-TGFbR (e.g., SEQ ID NOs: 390, 22); anti-CD47-SIGLEC10 (e.g., SEQ ID NOs: 389, 22); anti-CD47-VEGFR (e.g., SEQ ID NOs: 392, 22); anti-CD47-BTLA (e.g., SEQ ID NOs: 383, 22); anti-CD47-PD1 (e.g., SEQ ID NOs: 387, 22); anti-CD47-TIM3 (e.g., SEQ ID NOs: 391, 22). In another embodiment, the fusion protein comprises antibody that binds SIRPa or CD47 fused to one receptor ECD on heavy chain and another receptor ECD fused on light chain.

In various embodiments, the fusion proteins of the invention counteract SIGLEC10/CD24 in the tumor microenvironment.

In various embodiments, the fusion protein comprises a ligand-binding sequence of an extracellular domain of SIGLEC10 (SIGLEC10 ECD). In some embodiments, the fusion protein comprises an antibody and SIGLEC10 ECD. In one embodiment, the SIGLEC10 ECD is fused to the heavy chain of the antibody. In another embodiment, the SIGLEC10 ECD is fused to the light chain of the antibody. In a preferred aspect, SIGLEC10 ECD is fused to C terminus of antibody heavy chain or light chain. In another aspect, SIGLEC10 ECD is fused to N terminus of antibody heavy chain or light chain.

In some embodiments, the fusion protein comprises SIGLEC10 ECD and a polypeptide that inhibits the interaction between CD47 and SIRPa. In one embodiment, this fusion protein is anti-CD47 mAb fused to SIGLEC10 ECD (e.g., anti-CD47-SIGLEC10 (e.g., SEQ ID NOs: 389, 22)). In another embodiment, this fusion protein comprises SIRPa ECD and SIGLEC10 ECD. In one embodiment, this fusion protein is SIRPa-Fc-SIGLEC10 (e.g., SEQ ID NO: 549) or SIGLEC10-Fc-SIRPa (e.g., SEQ ID NO: 543).

In a further aspect, the fusion protein comprises SIGLEC10 ECD, a polypeptide that inhibits the interaction between CD47 and SIRPa, and another polypeptide that inhibits a T cell co-inhibitory molecule. In some embodiments, this fusion protein comprises anti-CD47 mAb with SIGLEC10 ECD fused to the heavy chain or light chain; and the ECD of an immuno-inhibitory molecule fused to the other chain. In a preferred embodiment, the immuno-inhibitory molecule suppresses immune cells via ITIM/ITSMs. In a particular embodiment, this fusion protein is anti-CD47-SIGLEC10-TIM3 (e.g., SEQ ID NOs: 389, 386); anti-CD47-SIGLEC10-BTLA (e.g., SEQ ID NOs: 389, 388).

In another aspect, the fusion protein comprises SIGLEC10 ECD, anti-CD47 mAb, and VEGFR ECD. In some embodiments, VEGFR ECD is fused to heavy chain of anti-CD47 mAb and SIGLEC10 ECD is fused to light chain of anti-CD47 mAb. In one embodiment, this fusion protein is anti-CD47-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 392, 385).

In another aspect, the fusion protein comprises SIGLEC10 ECD, PD1 ECD, and an targeting polypeptide that is an antibody with a heavy chain and light chain. In one aspect, the SIGLEC10 ECD is fused to the heavy chain of the antibody and the PD1 ECD is fused to the light chain of the antibody. Exemplary embodiments include anti-CTLA4-SIGLEC10-PD1 (e.g., SEQ ID NOs: 442, 436), anti-TIM3-SIGLEC10-PD1 (e.g., SEQ ID NOs: 488, 482), anti-PDL1-SIGLEC10-PD1, anti-EGFR-SIGLEC10-PD1 (e.g., SEQ ID NOs: 227, 221), anti-HER2-SIGLEC10-PD1 (e.g., SEQ ID NOs: 251, 245), anti-EGFRvIII-SIGLEC10-PD1 (e.g., SEQ ID NOs: 239, 233), anti-uPAR-SIGLEC10-PD1, anti-PSMA-SIGLEC10-PD1, anti-TGFb-SIGLEC10-PD1 (e.g., SEQ ID NOs: 400, 394), anti-TGFbR-SIGLEC10-PD1, and anti-GARP-SIGLEC10-PD1, anti-VEGF-SIGLEC10-PD1 (e.g., SEQ ID NOs: 368, 362), and anti-VEGFR-SIGLEC10-PD1 (e.g., SEQ ID NOs: 379, 373).

In some embodiments, the fusion protein comprises SIGLEC10 ECD and a polypeptide that inhibits a T cell co-inhibitory molecule. In specific embodiments, the fusion protein comprises SIGLEC10 ECD and an antibody that binds and disables a T cell co-inhibitory molecule. Exemplary embodiments include anti-PDL1-SIGLEC10 (e.g., SEQ ID NOs: 463, 109); anti-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 488, 141); anti-PD1-SIGLEC10 (e.g., SEQ ID NOs: 454, 101); anti-CTLA4-SIGLEC10 (e.g., SEQ ID NOs: 442, 28); anti-TIGIT-SIGLEC10 (e.g., SEQ ID NOs: 476, 139). Additional exemplary embodiments are anti-PDL1 mAb fused to SIGLEC10 ECD where the anti-PDL1 mAb is atezolizumab (SEQ ID NOs: 108, 109); avelumab (SEQ ID NOs: 110, 111); durvalumab (SEQ ID NOs: 112, 113). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIRPa ECD, PD1 ECD, TGFbRII ECD, TIM3 ECD, BTLA ECD, VEGFR ECD.

In some embodiments, the fusion protein comprises an antibody that binds a T cell co-stimulatory molecule fused to SIGLEC10. This antibody is preferably an agonist of the T cell co-stimulatory molecule. In some embodiments, this fusion protein is selected from: anti-41BB-SIGLEC10 (e.g., SEQ ID NOs: 500, 2); anti-OX40-SIGLEC10 (e.g., SEQ ID NOs: 512, 97); anti-ICOS-SIGLEC10 (e.g., SEQ ID NOs: 524, 59). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIRPa ECD, PD1 ECD, TGFbRII ECD, TIM3 ECD, BTLA ECD, VEGFR ECD.

In one embodiment, the fusion protein comprises SIGLEC10 ECD and a polypeptide that binds either CD39 or CD73. In some embodiments, the fusion protein is an antibody that binds CD39 or CD73 fused to SIGLEC10 ECD; for example: anti-CD39-SIGLEC10 (e.g., SEQ ID NOs: 430, 18) or anti-CD73-SIGLEC10 (e.g., SEQ ID NOs: 423, 24). In some embodiments, the fusion protein comprises an additional receptor ECD fused to the antibody selected from [ECD]. In some embodiments, the fusion protein is selected from the following: anti-CD73-SIGLEC10-PD1 (e.g., SEQ ID NOs: 423, 417); anti-CD73-SIGLEC10-TIM3 (e.g., SEQ ID NOs: 423, 420); anti-CD73-SIGLEC10-SIRPa (e.g., SEQ ID NOs: 423, 419); anti-CD73-SIGLEC10-BTLA (e.g., SEQ ID NOs: 423, 422).

In some embodiments, the fusion protein comprises a tumor-targeted antibody and SIGLEC10 ECD. In some embodiments, this tumor targeted-antibody binds a tumor growth factor, growth factor receptor, or tumor cell surface molecule. In some embodiments, this fusion protein is selected from the following: anti-EGFR-SIGLEC10 (e.g., SEQ ID NOs: 227, 43), anti-HER2-SIGLEC10 (e.g., SEQ ID NOs: 251, 55), anti-EGFRvIII-SIGLEC10 (e.g., SEQ ID NOs: 239, 47), anti-uPAR-SIGLEC10 (e.g., SEQ ID NOs: 270, 162), anti-PSMA-SIGLEC10 (e.g., SEQ ID NOs: 277, 121), anti-nectin4-SIGLEC10 (e.g., SEQ ID NOs: 263, 160). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIRPa ECD, PD1 ECD, TGFbRII ECD, TIM3 ECD, BTLA ECD, VEGFR ECD.

In some embodiments, the fusion protein comprises SIGLEC10 ECD and an antibody that binds IL-17/IL-17R, IL-23/IL-23R, or IL-6/IL-6R. In a preferred embodiment, the antibody interrupts the interaction between the ligand and receptor. In some embodiments, the fusion protein is selected from the following: anti-IL17-SIGLEC10, anti-IL17R-SIGLEC10 (e.g., SEQ ID NOs: 332, 63), anti-IL23-SIGLEC10 (e.g., SEQ ID NOs: 344, 75), anti-IL23R-SIGLEC10, anti-IL6-SIGLEC10, anti-IL6R-SIGLEC10 (e.g., SEQ ID NOs: 320, 79). In a further embodiment, the fusion protein may comprise an additional ECD of an immuno-inhibitory receptor selected from SIRPa ECD, PD1 ECD, TGFbRII ECD, TIM3 ECD, BTLA ECD, VEGFR ECD.

In some embodiments, the fusion protein comprises SIGLEC10 ECD and an antibody that binds TGFb, TGFbR, or GARP. Exemplary embodiments of this fusion protein include anti-TGFb-SIGLEC10 (e.g., SEQ ID NOs: 400, 133), anti-TGFbR-SIGLEC10, and anti-GARP-SIGLEC10 (e.g., SEQ ID NOs: 412, 49). In some embodiments, the fusion protein further comprises an additional receptor ECD. Exemplary embodiments of this fusion protein include anti-TGFb-SIGLEC10-TIM3 (e.g., SEQ ID NOs: 400, 397); anti-TGFb-SIGLEC10-PD1 (e.g., SEQ ID NOs: 400, 394); anti-TGFb-SIGLEC10-SIRPa (e.g., SEQ ID NOs: 400, 396); anti-TGFb-SIGLEC10-BTLA (e.g., SEQ ID NOs: 400, 399).

In some embodiments, the fusion protein comprises SIGLEC10 ECD and IL-15 ECD or IL-12 ECD. In some embodiments, the fusion protein is IL15-Fc-SIGLEC10 (e.g., SEQ ID NO: 582), SIGLEC10-Fc-IL15 (e.g., SEQ ID NO: 581), IL12-Fc-SIGLEC10 (e.g., SEQ ID NO: 580) or SIGLEC10-Fc-IL12 (e.g., SEQ ID NO: 579).

In some embodiments, the fusion proteins of the invention comprise a targeting polypeptide that binds SIGLEC10 or CD47 fused to one or more receptor ECDs. These receptor ECDs are preferably selected from the following: TIM3 ECD, BTLA ECD, VEGFR ECD, TGFbRII ECD, PD1 ECD, SIRPa ECD. In some embodiments, the targeting polypeptide that binds SIGLEC10 or CD47 is an antibody. Exemplary embodiments include anti-CD47-TGFbR (e.g., SEQ ID NOs: 390, 22); anti-CD47-SIGLEC10 (e.g., SEQ ID NOs: 389, 22); anti-CD47-VEGFR (e.g., SEQ ID NOs: 392, 22); anti-CD47-BTLA (e.g., SEQ ID NOs: 383, 22); anti-CD47-PD1 (e.g., SEQ ID NOs: 387, 22); anti-CD47-TIM3 (e.g., SEQ ID NOs: 391, 22). In another embodiment, the fusion protein comprises antibody that binds SIGLEC10 or CD47 fused to one receptor ECD on heavy chain and another receptor ECD fused on light chain.

In one embodiment the present invention provides methods of treating cancer by administering agent(s) that counteract multiple ligand/receptor interactions that promote tumor angiogenesis and/or immune dysfunction in the tumor microenvironment (TME).

The molecules of the invention may be used for the treatment of cancer. Further, the molecules of the invention may be used in conjunction or in combination with any other type of therapy including surgery, chemotherapy, radiation therapy, targeted small molecules, anti-angiogenic therapy or immunotherapy. Immunotherapy may include any immuno-oncologic drug selected from a broad range of agents, including antibodies, vaccines, adjuvant therapies, cytokines, oncolytic viruses, bispecific molecules, and cellular therapies. In a specific embodiment, the molecules of the invention may be administered to a subject in combination with (Chimeric Antigen Receptor (CAR) T cell therapy. In various aspects, the molecules of the invention may be administered in combination with one or more different molecules of the invention. In various aspects, the molecules of the invention may be administered prior to, concurrently, sequentially, and/or following another therapy. In various aspects, the molecules of the invention may be administered in a composition with any other therapeutic agent or molecule of the invention.

In some embodiments, molecules of the invention alone or in combination with other therapies counteract immune tolerance in the tumor microenvironment. In some embodiments, molecules of the invention alone or in combination with other therapies counteract angiogenesis in the tumor microenvironment.

In various embodiments, a subject may be administered one or more molecules from one or more of the following types of fusion proteins of the invention: fusion protein comprising an anti-VEGF antibody or anti-VEGFR antibody or VEGF-binding sequence of VEGFR ECD; fusion protein comprising anti-TGFb antibody or TGFb-binding sequence of TGFbR ECD; fusion protein comprising anti-PD1 antibody or anti-PDL1 antibody or PD1-binding sequence of PD1 ECD; fusion protein comprising anti-BTLA antibody or anti-HVEM antibody or HVEM-binding sequence of BTLA ECD; fusion protein comprising anti-CEACAM antibody or anti-TIM3 antibody or CEACAM-binding sequence of TIM3 ECD; fusion protein comprising anti-CD47 antibody or anti-SIRPa antibody or CD47-binding sequence of SIRPa ECD; fusion protein comprising anti-CD24 antibody or anti-SIGLEC10 antibody or CD24-binding sequence of SIGLEC10 ECD.

In one embodiment, the present invention provides method of treating a subject having a disease or disorder comprising administering to the subject a fusion protein of the invention. In certain embodiments the patient has cancer.

In various embodiments, a subject may be administered one or more fusion proteins described in the invention. In some embodiments, the fusion proteins comprise one or more of TGFbRII ECD, VEGFR ECD, PD1 ECD, BTLA ECD, SIRPa ECD, TIM3 ECD, and SIGLEC10 ECD.

In various embodiments, a subject may be administered one or more fusion proteins described in the invention in combination with a polypeptide that disables an immune cell inhibitory molecule or T cell co-inhibitory molecule (e.g., CTLA-4, BTLA, TIM-3, CEACAM1, or CEACAM-5, TIGIT, PVRIG, VISTA, VSIG8, LAG-3, CD47, SIRPa, CD24, SIGLEC10, or LILRB1). In some embodiments, this polypeptide is an antibody. In other embodiments, the polypeptide is a fusion protein comprising the ECD of a T cell co-inhibitory molecule. In some embodiments, this polypeptide may be PD1-Fc, TIM3-Fc, or BTLA-Fc. In some embodiments, the polypeptide may be an anti-PD¹/anti-PDL1 mAb. Exemplary such antibodies are anti-PD1 (e.g., nivolumab, pembrolizumab) and anti-PDL1 (e.g., durvalumab, avelumab, atezolizumab).

In various embodiments, a subject may be administered one or more fusion proteins described in the invention in combination with a second fusion protein described in the invention. In various aspects, this second fusion protein disables a T cell co-inhibitory molecule. In some embodiments, this second fusion protein comprises BTLA ECD, TIM-3 ECD, or PD-1 ECD.

In various embodiments, a subject may be administered one or more fusion proteins described in the invention in combination with an antibody or fusion protein that activates an T cell co-stimulatory molecule (e.g., OX40, 41BB, ICOS, GITR, HVEM, CD27, CD40, CD30, DNAM). In some embodiments, the fusion protein comprises the ECD of a T cell co-stimulatory ligand (e.g., OX40L, 41BBL, ICOSL, GITRL, LIGHT, CD70, CD40L, CD30L) that binds a T cell co-stimulatory receptor as an agonist.

In various embodiments, a subject may be administered one or more fusion proteins described in the invention in combination with an inhibitor of TGFb/TGFbR. In some aspects, this TGFb/TGFbR inhibitor is selected from: a-TGFb antibody; a-TGFbR antibody; TGFbRII ECD containing fusion protein (e.g. TGFbRIIecd-Fc); TGFbR TKI (e.g. galunisertib); anti-GARP antibody; anti-LAP antibody; ALT comprising TGFbRII ECD; ALT that inhibits TGFb/TGFbR; fusion proteins described in this invention that inhibit TGFb/TGFbR.

In various embodiments, a subject may be administered one or more fusion proteins described in the invention in combination with an inhibitor of VEGF/VEGFR. In some aspects, the VEGF/VEGFR inhibitor may be selected from: anti-VEGF antibody (e.g., bevacizumab), anti-VEGFR antibody (e.g. ramucirumab), VEGFR kinase inhibitor (e.g., sunitinib, sorafenib, axitinib, cabozantinib, regorafenib, pazopanib, vandetanib, lenvatenib), or VEGFR ECD-Fc fusion protein (e.g., aflibercept).

In various embodiments, a subject may be administered one or more fusion proteins described in the invention in combination with an inhibitor of TH17 differentiation and/or function. In some aspects, this agent is an inhibitor of the interaction between IL23/IL23R, IL1/IL1R, IL6/IL6R, or IL17/IL17R. In some aspects, this agent is selected from: anti-IL17R antibody, anti-IL17 antibody, anti-IL17 nanobody; anti-IL6R antibody, anti-IL6 antibody; IL23 antibody, anti-IL23R antibody; anti-IL1R antibody, anti-IL1 antibody. In other aspects, this agent is a fusion protein described in the invention that inhibits IL23/IL23R, IL1/IL1R, IL6/IL6R, IL17/IL17R.

In various embodiments, a subject may be administered one or more fusion proteins described in the invention in combination with an immunocytokine or cytokine fusion protein comprising an active ligand or ligand fragment of IL12 or IL15.

In various embodiments, a subject may be administered one or more fusion proteins described in the invention in combination with a polypeptide that binds a tumor cell- or tumor antigen, tumor growth factor or growth factor receptor. In one aspect, this polypeptide is an antibody. In another aspect, this polypeptide is conjugated to a cytotoxic compound. In a further aspect, this polypeptide is an ADC. In a further aspect, this polypeptide is an ALT-DC.

In various embodiments, a subject may be administered one or more fusion proteins described in the invention in combination with a chimeric antigen receptor T cell (CAR T cell)

In various embodiments, a subject may be administered one or more fusion proteins described in the invention in combination with an immunotherapeutic agent.

In various embodiments, a subject may be administered one or more fusion proteins described in the invention in combination with an inhibitor of tumor cell signaling that promotes tumor cell survival, proliferation, invasion, and/or metastases; tumor angiogenesis; or immune dysfunction in the TME.

In various embodiments, a subject may be administered one or more fusion proteins described in the invention in combination with a chemotherapeutic or cytotoxic agent, a DNA repair inhibitor or PARP inhibitor, a tumor vaccine or viriolytic agent; or ionizing radiation.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a Schematic representation of anti-PDL1-BTLA ECD and anti-PDL1-TGFbRII ECD-BTLA ECD.

FIGS. 2A-2B show antibody-ligand traps containing BTLA ECD localize to HVEM-expressing cells and simultaneously counteract BTLA-mediated suppression & promote HVEM-mediated activation of T cells. BTLA ligation by HVEM inhibits T cell activation via SHP-1-mediated inhibition of CD28 and CD3z signaling. HVEM ligation by LIGHT or BTLA (in trans) promotes T cell activation. The antibody ligand traps of the invention comprising a BTLA ECD which binds HVEM, thereby disrupting its interaction with both BTLA and CD160. In addition, ligation of T cell HVEM by BTLA ECD of the ALT may promote HVEM-mediated costimulatory signals for T cell activationPD-1 ligation by PD-1 ligands (PD-L1 or PD-L2) inhibits T cell activation via SHP-2-mediated inhibition of CD28 signaling. The interaction of PD-L1 with PD-1 can be disrupted by antibodies targeting either PD-L1 or PD-1, or a PD1 ECD that binds both PD-L1 and PD-L2. Antibody ligand traps comprising a BTLA ECD fused to an antibody that specifically binds PD-L1, or PD-1 can simultaneously inhibit PD-L1/PD-1 and HVEM/BTLA induced SHP1/2 mediated suppression of CD28 and CD3 signaling. As such, these molecules of the invention can counteract both HVEM/BTLA and PD-L1 mediated immune suppression in the tumor environment, thereby enhancing antitumor immune responses.

FIGS. 3A-3B show the characterization of a-PDL1-BTLA ECD, a-PDL1-TGFbRII and a-PDL1-TGFbRII ECD-BTLA ECD. 3A: SDS-PAGE under reducing (R) and non-reducing (NR) conditions was used to compare the full-length (FL), heavy chain (HC) and light chain (LC) of anti-PDL1 (atezolizumab), anti-PDL1-BTLA ECD and anti-PDL1-TGFbRII ECD-BTLA ECD. 3B: SEC-HPLC analysis of anti-PDL1 (atezolizumab), anti-PDL1-BTLA ECD and anti-PDL1-TGFbRII; ECD-BTLA ECD (>99% monomericity).

FIGS. 4A-4D show the target binding ability of a-PDL1-BTLA ECD, a-PDL1-TGFbRII and a-PDL1-TGFbRII ECD-BTLA ECD. 4A: Standard ELISA showing the ability of anti-PDL1 (atezolizumab), anti-PDL1-BTLA ECD and anti-PDL1-TGFbRII ECD-BTLA ECD to bind PD-L1. 4B: Standard ELISA showing the ability of anti-PDL1-TGFbRII ECD and anti-PDL1-TGFbRII ECD-BTLA ECD to bind TGFb. 4C: Standard ELISA showing the ability of; anti-PDL1-BTLA ECD and anti-PDL1-TGFbRII ECD-BTLA ECD to bind the BTLA ligand HVEM. 4D: ELISA showing the ability of anti-PDL1-BTLA ECD and anti-PDL1-TGFbRII ECD-BTLA ECD to simultaneously bind PD-L1 and the BTLA ligand HVEM.

FIGS. 5A-5C show anti-PDL1, and anti-PDL1-BTLA ECD activity. 5A: Ability of anti-PDL1, anti-PDL1-BTLA ECD to elicit antitumor immunity and inhibit the growth of syngeneic B16-F10 tumors in C57BL/6 muMt-mice. 5B: Ability of anti-PDL1, anti-PDL1-BTLA ECD to elicit antitumor immunity and inhibit the growth of cancers was examined in human immune reconstituted NSG mice bearing human WiDR-colorectal cancer cells. 5C: Ability of anti-PDL1, anti-PDL1-BTLA ECD, anti-PDL1-TGFbRII ECD and anti-PDL1-BTLA ECD-TGFbRII ECD to elicit antitumor immunity and inhibit the growth of cancers was examined in human immune reconstituted NSG mice bearing human BXPC3-pancreatic cancer cells.

FIGS. 6A-6C show a-VEGF-PD1 activity. 6A: Mice are treated with mAbs 24 h prior to the radiotracer injection. 6B: CD3+ are counted in immunohistochemistry images of tumors in control group. anti-VEGF group, or anti-VEGF-PD1 ECD group. 6C: NSG mice immune reconstituted with tumor-matched HLA A2+ human CD34+ HSC and bearing KRAS mutant D-MUT1 human colorectal cancer tumor xenografts were treated (5 mg/kg i.p. weekly) with vehicle alone (untreated control) or the following antibodies (either alone or in combination), as indicated: with either vehicle alone (untreated control) or the following antibodies: a-VEGF-PD1 ECD; a-VEGF (bevacizumab.

FIGS. 7A-7C show a-VEGF-TGFbRII-PD1 activity. 7A: Structure of anti-VEGF-TGFbRII-PD1. anti-VEGF binds VEGF, TGFbRII binds TGFb, PD1 binds PD-L1 and PD-L2. 7B: NSG mice immune were reconstituted with tumor-matched HLA A2+ human CD34+ HSC followed by subcutaneous implantation of WiDR tumor xenografts. 7C: NSG mice immune were reconstituted with tumor-matched HLA A2+ human CD34+ HSC followed by subcutaneous implantation of BXPC3 tumor xenografts.

FIGS. 8A-8C show a-VEGF-TGFbRII-PD1 activity. 8A: Standard ELISA showing the ability of anti-VEGF (bevacizumab), anti-VEGF-TGFbRII-PD1 to bind VEGF. 8B: Standard ELISA showing the ability of anti-VEGF-TGFbRII-PD1 to bind TGFb. 8C: Standard ELISA showing the ability of anti-VEGF-TGFbRII-PD1 to bind TGFb as well as IgG-TGFbRII.

FIGS. 9A-9C shows anti-HER2-TGFbRII and anti-HER2-PD1 activity. 9A: SDS-PAGE under reducing (R) and non-reducing (NR) conditions was used to compare the full-length (FL), heavy chain (HC) and light chain (LC) of anti-HER2-TGFβRIIECD, anti-HER2-PD1 ECD, and anti-HER2 (Trastuzumab). 9B: The ability of anti-HER2-TGFβRII to simultaneously bind HER2 and TGF-β1 was evaluated by a ‘double-sandwich’ ELISA wherein anti-HER2-TGFβRIIECD was added to HER2-Fc coated plates, followed by rhTGF-β1 (1 ng/ml) that was detected by a biotinylated anti-huTGF-β1 antibody. 9C: The ability of anti-HER2-TGFβRII to bind TGF-β1 was also evaluated by competition immunoassays.

FIGS. 10A-10B show anti-HER2-TGFbRII activity. 10A: Residual tumors in TrastuzumabR BT-474 (BT-474-TR) F2 tumor-bearing mice following treatment with anti-HER2-TGFβRII were significantly smaller (mean±SEM=31.7±6.5) than those in F2 mice treated with anti-HER2 mAb (mean±SEM=453.9±121.4) (p=0.003). 10B: Serum was collected from TrastuzumabR BT-474 tumor-bearing mice.

FIGS. 11A-11C show a-EGFR-TGFbRII activity. 11A: Human tumor xenografts were generated by mammary fat pad implantation of the MDA-MB-231-Luc (D3H2LN) TNBC line in female immune deficient NOG mice (NOD/Shi-scid IL-2rgnull). 11B: Immune deficient NSG mice (NOD/Shi-scid IL-2rgnull; 6-8 weeks old) were irradiated at 200 cGy and rested for 6-8 h, followed by adoptive transfer of human CD34+ cells (7×104/mouse) from a normal donor (HLA-matched to the D-MUT1 line)(ALLCELLS). 11C: Nude mice were inoculated subcutaneously with a PDX of human HNSCC (SCC harvested from the floor of the mouth).

FIGS. 12A-12B show anti-PD1-TIM3 and anti-PDL1-TIM3 activity. 12A: (top) Schematic of anti-PD1-TIM3 ECD and anti-PDL1-TIM3 ECD. Anti-PDL1-TIM3 ECD was designed to target both PD-L1 and TIM3 ligands by fusing the C-terminus of the heavy chain of an anti-PDL1 antibody with a ligand binding sequence of the extracellular domain of TIM3 (TIM3 ECD) via a flexible linker peptide, (GGGGS)3. 12B: (top) a-PD1-TIM3 ECD (430.3±29.9) inhibits tumor growth significantly more effectively than untreated control (908.2±40.3), a-PD-1 (824.0±38.3), IgG-TIM3 ECD (825.1±79.0) or the combination of IgG-TIM3 ECD and a-PD1 (884.7±97.4) (p<0.0001). 12 B: (bottom) a-PDL1-TIM3 ECD (226.4±71.4) inhibits tumor growth more effectively than a-PDL1 (617.5±144.3), a-TIM-3 (640.9±99.6) or the combination of a-TIM-3 and a-PDL1 mAbs (653.0±59.8) (p<0.001).

DETAILED DESCRIPTION OF THE INVENTION

Before the present compositions and methods are described, it is to be understood that this invention is not limited to particular compositions, methods, and experimental conditions described, as such compositions, methods, and conditions may vary. It is also to be understood that the terminology used herein is for purposes of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only in the appended claims.

As used in this specification and the appended claims, the singular forms “a”, “an”, and “the” include plural references unless the context clearly dictates otherwise. Thus, for example, references to “the method” includes one or more methods, and/or steps of the type described herein which will become apparent to those persons skilled in the art upon reading this disclosure and so forth.

All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the invention, it will be understood that modifications and variations are encompassed within the spirit and scope of the instant disclosure. The preferred methods and materials are now described.

In some embodiments, the targeting polypeptide is an antibody or other polypeptide comprising a heavy chain and light chain connected by one or more disulfide bonds. “X” is a molecule that is specifically bound by this targeting polypeptide. “Y” is a ligand-binding sequence of an extracellular domain, or fragment thereof “Z” is a ligand-binding sequence of a different extracellular domain, or fragment thereof. In some embodiments, the fusion proteins of the invention have the structure “anti-{X}-{Y}-{Z}”, where Y and Z are fused to the polypeptide that binds X. In some embodiments, Y is fused to the C terminus of the heavy chain of the antibody and Z is fused to the C terminus of the light chain of the antibody. In other embodiments, Y is fused to the C terminus of the light chain of the antibody and Z is fused to the C terminus of the heavy chain of the antibody. In some embodiments, Y is fused to the N terminus of the heavy chain of the antibody and Z is fused to the N terminus of the light chain of the antibody. In other embodiments, Y is fused to the N terminus of the light chain of the antibody and Z is fused to the N terminus of the heavy chain of the antibody.

In some embodiments, the ECD is fused to the C terminus of the antibody heavy chain or light chain. In other cases, the ECD may be fused to the N terminus of the antibody heavy chain or light chain.

In some embodiments, the fusion proteins comprise two ECDs (ECD #1, ECD #2) fused together. Fusion proteins that comprise two ECDs fused together may be referred to as “ECD-ECD”s in this invention. In some embodiments, the fusion protein additionally comprises a Fc domain. In some embodiments, the fusion protein additionally comprises a linker. In some embodiments, the structure of the fusion protein is N (terminus)-ECD #1-ECD #2-C (terminus). In other embodiments, the structure is N-ECD #2-ECD #1-C. In other embodiments, the structure is N-ECD #1-linker-ECD #2-C or N-ECD #2-linker-ECD #1-C. In other embodiments, the structure is N-ECD #1-Fc-ECD #2-C or N-ECD #2-linker-ECD #1-C. In other embodiments, the structure is N-ECD #1-Fc-linker-ECD #2-C, or N-ECD #2-Fc-linker-ECD #1-C.

In one aspect, two or more ECDs may be fused in serial. In one aspect, the fusion protein comprises a targeting polypeptide and two or more ECDs are fused in serial on the same chain of the targeting polypeptide. In one aspect, two or more ECDs are fused in serial on the light chain of a targeting polypeptide that is an antibody. In one aspect, the two or more ECDs are connected by linkers. For example, the light chain of a fusion protein of the invention might be N terminus-antibody light chain-linker-ECD #1-linker-ECD #1-C terminus. In another aspect, the ECD may be fused to both the N and C terminii of the same chain. For example, the light chain of a fusion protein of the invention might be N terminus-ECD #1-linker-antibody light chain-linker-ECD #1-C terminus.

“Reeptor ECD”, “extracellular domain”, “ECD”, “ECD”, “ligand trap” and “LT” are used interchangeably in this invention. In any case where any of these terms are used, they may also refer to any ligand-binding sequence of the extracellular domain or fragment thereof in question.

The ECD(s), or “ligand traps”, of the fusion protein enable one or more of the following functions: (1) sequestration of ligands/cytokines that contribute to angiogenesis in the tumor microenvironment; (2) sequestration of ligands/cytokines that promote tumor cell survival, proliferation, invasion, and/or metastasis; (3) sequestration of ligands/cytokines that contribute to tumor-induced immune tolerance or immune dysfunction; (4) activation of a T cell co-stimulatory molecule; (5) inhibition of a T cell co-inhibitory molecule; (5) preferential localization to the target tissue/cell microenvironment expressing its cognate ligand(s).

N-glycosylation occurs at the following consensus sites: NX1S or NX1T, where X1 is any amino acid that is not proline. N is asparagine, S is serine, and T is threonine. More rarely, N-glycosylation can occur at NX2C where N is asparagine, X2 is any amino acid, and C is cysteine. In some embodiments, one or more N-glycosylation consensus sites may be mutated to reduce glycosylation of the ligand trap. In some embodiments, hypoglycosylation of the ligand trap is achieved by mutation of an asparagine residue in a N-glycosylation consensus sequence to another polar amino acid (i.e., serine, threonine, or glutamine). In other embodiments, hypoglycosylation of the ligand trap is achieved by mutation of an asparagine residue in a N-glycosylation consensus sequence to alanine.

In various embodiments, the fusion proteins of the invention comprise one or more of the following ECDs: (1) a ligand-binding sequence of an extracellular domain of TGFbR (e.g., TGFbRII ECD), or fragment thereof. In one aspect, this ECD binds TGFb1, TGFb2, and/or TGFb3; (2) a ligand-binding sequence of an extracellular domain of PD-1 (e.g., PD1 ECD), or fragment thereof. In one aspect, this ECD binds PD-L1 and/or PD-L2. In one embodiment, this ligand trap has one or more amino acid substitutions which increase its affinity for PD-L1 and/or PD-L2; (3) a ligand-binding sequence of an extracellular domain of VEGFR (e.g., VEGFR1, VEGFR2, VEGFR3), or fragment thereof, or a fusion of VEGF-binding sequences of one or more VEGFR extracellular domains (e.g., VEGFR1 domain 2 fused to VEGFR2 domain 3). In one aspect, this ECD binds VEGFA, VEGFB, VEGFC, and/or PIGF; (4) a ligand-binding sequence of an extracellular domain of TIM-3 (e.g., TIM3 ECD), or fragment thereof, or a hypoglycosylated variant of TIM-3, or fragment thereof. In one aspect, this ECD binds CEACAM1, CEACAM5, phosphatidyl-serine, and/or Galectin-9; (5) a ligand-binding sequence of an extracellular domain of SIRPa (e.g., SIRPa-ECD), or fragment thereof; or a hypoglycosylated variant of SIRPa, or fragment thereof. In one aspect, this ECD binds CD47; (6) a ligand-binding sequence of an extracellular domain of B- and T-lymphocyte attenuator (BTLA ECD) or fragment thereof, or a hypoglycosylated variant of BTLA or fragment thereof. In one aspect, this ECD binds herpesvirus entry mediator (HVEM); (7) a ligand-binding sequence of an extracellular domain of SIGLECi0 or fragment thereof, or a hypoglycosylated variant of SIGLECi0 or fragment thereof. In one aspect, this ECD binds CD24.

In one embodiment, the fusion protein comprises a ligand-binding sequence of an extracellular domain of TGFbR (e.g., TGFbRII ECD) or fragment thereof to bind and disable TGFb in the target cell microenvironment. In some embodiments, the TGFbR ECD may be a ligand-binding sequence of TGFbRII ECD. In some embodiments, the TGFbR ECD may be a fusion of domains from TGFbRII and TGFbRIII. In some embodiments, the TGFbR ECD may be selected from the following list: SEQ ID NOS: 177; 178; 179; 180. TGFβ inhibits the expression of cytotoxic effector molecules in immune cells and suppresses their ability to induce antibody-mediated ADCC of tumor cells. TGFb results in a significant decrease in their expression of several cytotoxic effector molecules, including granzyme B, Apo2L/TRAIL, CD95L/FasL, and IFN-γ. TGFb inhibits T cell-mediated antitumor immunity. TGF suppresses the expression of interferon-gamma (IFNgamma), restricts the differentiation of TH1 cells, attenuates the activation and cytotoxic function of CD8+ effector cells, and inhibits the development of central memory T cells. Most significantly, TGFb induces the differentiation of regulatory T cells (Tregs), a sub-population of immunosuppressive CD4+ T cells that express the CD25 and FOXP3. TGFb induces the expression of FOXP3, the signature transcription factor that determines and maintains the functional program of the Treg lineage. Besides inhibiting NK cells and regulating T cell lineage determination and function, TGFb also promotes the polarization of pro-tumorigenic M2 macrophages which secrete high levels of TGFb, IL-6, and IL-10. As such, TGF counteracts the ability of tumor-targeted antibody to induce adaptive antitumor immunity via Fc-FcR mediated antigen cross-presentation by DCs. In one aspect, the ligand-binding sequence of TGFbRII ECD that is fused to a targeting antibody binds and traps TGFb1, TGFb2, and/or TGFb3. As such, a fusion protein of the invention comprising TGFbRII ECD thus uniquely sequesters TGFb1, TGFb2, and TGFb3 in the tumor or target microenvironment in such a way that all immunosuppressive, angiogenic, and tumor-promoting effects of TGFb are blocked in the target or tumor cell microenvironment.

In one embodiment, the fusion protein comprises a ligand-binding sequence of an extracellular domain of Programmed Death-1 (PD-1 ECD) or fragment thereof to bind and disable PD-1 ligands (PD-L1 or PD-L2) in the target cell microenvironment. Upregulation of Programmed death-1 ligands (PD-L1, PD-L2) is a major common denominator of immune tolerance via suppression of natural killer (NK) cell and T cell-mediated antitumor immunity. Engagement of PD-1 by its ligands [PD-L1 (B7-H1); PD-L2 (B7-DC)], inhibits the proliferation, survival, and function of T cells, and cooperates with TGF-b to promote the differentiation and function of Tregs. Tumor cell expression of PD-1 ligands in the tumor microenvironment inhibits activation of tumor infiltrating T cells via interaction of PD-L1 and PD-L2 with either PD-1 or B7. PD1 ECD completely sequesters both PD-L1 and PD-L2, preventing either ligand from interacting with PD-1 on T cells/NK cells or CD80/86 on DCs. This complete inhibition of all PD-1 ligand activity is not recapitulated by either anti-PD1 or anti-PDL1 antibodies: anti-PDL1 has no effect on PD-L2 signaling; and anti-PD1 has no effect on PD-L1/2 binding to CD80/86 on DCs. In one aspect, the ligand-binding sequence of PD1 ECD that is fused to a targeting antibody binds and traps PD-L1 and/or PD-L2. In one aspect, the PD-1ECD fused to the targeting antibody comprises a PD-1ECD sequence incorporating specific mutations in residues to increase the affinity to PD-L1 and/or PD-L2 (high affinity PD-1ECD). As such, the fusion protein comprising a fused PD-1ECD uniquely sequesters both PD-L1 and PD-L2 in the tumor microenvironment in such a way that all immunosuppressive effects of PD-L1/2 are blocked in the target cell microenvironment. In some embodiments, the PD1 ECD may be selected from the following list: SEQ ID NOS: 169; 170; 171

In one embodiment, the fusion protein comprises a ligand-binding sequence of an extracellular domain of Vascular endothelial growth factor receptor (VEGFR1 and/or VEGFR2) or fragment thereof to bind and disable VEGF in the target cell microenvironment. VEGF induces angiogenesis and immune suppression in the tumor microenvironment. VEGF is a high-affinity ligand for receptor tyrosine kinases VEGFR1, VEGFR2, and VEGFR3. VEGFA mRNA is overexpressed in most human tumors, where its expression correlates with invasiveness, increased vascular density, metastasis, tumor recurrence and poor prognosis. Tumors frequently harbor intrinsic genetic alterations that activate signaling pathways (RAS/MAPK, PI3K/AKT, or STAT3) leading to hypoxianti-inducible factor 1 (HIF-1)-mediated induction of VEGF expression in the tumor microenvironment. In addition, specific cytokines (IL-6, TGFb, IL-17) play a key role in increasing local levels of VEGF in the tumor immune microenvironment. VEGFA secreted by tumor cells and surrounding stroma stimulates the proliferation and survival of endothelial cells, leading to the formation of new blood vessels. In addition to secreting VEGF, tumors themselves express VEGF-R1 and VEGF-R2. VEGF promotes tumor migration and metastasis, via autocrine/paracrine stimulation of angiogenesis, cancer stem cell renewal and stability. VEGF also plays an angiogenesis-independent role in cancer immune evasion. VEGF inhibits anti-tumor immunity on multiple levels including promotion and expansion of inhibitory immune cells, such as myeloid-derived suppressor cells (MDSC), suppression of dendritic cell (DC) maturation, mitigation of effector T cell responses, and alteration of lymphocyte development and trafficking. In one aspect, the fusion protein comprises a ligand-binding sequence of VEGFR ECD that binds VEGFR ligands, (VEGF-A, VEGF-B) and optionally placental growth factor (PIGF), and prevents these ligands from binding their endothelial receptors, VEGFR-1 and VEGFR-2. In one aspect, the fusion protein comprises the vascular endothelial growth factor (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2. In one aspect, the VEGF trap comprises Ig domain 2 from VEGFR1, fused to Ig domain 3 from VEGFR2. In one embodiment, the fusion protein comprises amino acids 103-204 of VEGFR1 fused to amino acids 206-308 of VEGFR2. In one embodiment, the fusion protein comprises the same domains of VEGFR1 and VEGFR2 as aflibercept. In some embodiments, the VEGFR ECD may be selected from the following list: SEQ ID NOS: 184; 185; 186

In one embodiment, the fusion protein comprises a ligand-binding sequence of an extracellular domain of TIM-3 (TIM3 ECD) or fragment thereof to bind and disable TIM-3 ligands (CEACAM1, CEACAM5) in the target cell microenvironment. TIM-3 and CEACAM1 are transmembrane proteins expressed on activated T cells, and their expression is induced by cytokines involved in effector T cell differentiation (e.g., IFNgamma). CEACAM1 suppresses T cell activity via homodimerization of its extracellular domains in cis or trans (CEACAM1/CEACAM1). This homophilic interaction is required for phosphorylation of CEACAM1 cytoplasmic domain ITIMs and recruitment of the SHP-1/SHP-2 tyrosine phosphatases which effect proximal suppression of TCR signaling and inhibition of effector functions, including T cell proliferation, TH1 cytokine production and cytotoxicity. CEACAM1 also suppresses TCR signaling via binding TIM-3 along their shared signature “cleft.” The interaction of CEACAM1 with TIM-3 induces phosphorylation-mediated release of Bat3 and loss of Lck-mediated TCR signaling. CEACAM family members (CEACAM1, CEACAM5) are highly expressed in many tumor types, especially gastrointestinal adenocarcinomas (e.g., pancreatic cancer, colorectal cancer). Besides the cis interactions on T cells involving CEACAM1/TIM-3, CEACAM1 and CEACAM5 on tumor cells are able to induce exhaustion via trans interactions with CEACAM1 or TIM-3 on T cells. CEACAM family members also suppress the effector functions of innate immune cells. In one aspect, the ALT comprises a ligand-binding sequence of TIM-3ECD that binds CEACAM1 and/or CEACAM5. In another aspect, the TIM-3ECD sequence may contain mutations in amino acid residues that are normally glycosylated in order to reduce glycosylation at these sites. In one aspect, the fused TIM3 ECD serves as a decoy to sequester TIM-3 ligands (CEACAM1 and CEACAM5 on T cells and/or tumor cells), thereby disrupting cis and trans homodimeric and heterodimeric interactions of the CEACAM axis that lead to T cell exhaustion. Decoration of fusion protein-targeted cells in the TME with a decoy TIM-3ECD sequesters CEACAM family members by competing with native TIM-3 to bind the FG-CC′ cleft of CEACAM, enabling native TIM-3 on T cells to remain unligated and able to sustain Bat3/Lck-mediated T cell activation. In addition to counteracting T cell exhaustion, in another aspect the fusion protein comprising TIM3 ECD can simultaneously binds a tumor cell and CEACAM-1 on a T cell, thereby recruiting and sustaining tumor-reactive cytotoxic T cells in the tumor cell microenvironment.

In one embodiment, the ligand trap may be a ligand-binding sequence of an extracellular domain of TIM-3 (TIM3 ECD) or fragment thereof that is hypoglycosylated or deglycosylated (hypoglycosylated TIM-3 ECD or deglycosylated TIM-3 ECD). In some embodiments, any N-glycosylation consensus site of TIM3 ECD is mutated to reduce glycosylation of TIM3 ECD. In some embodiments, hypoglycosylation of the TIM3 ECD is achieved by mutations at one or more of the following sites: N78, V79, T80, N151, L152, and/or T153.

In some embodiments, hypoglycosylation of the TIM3 ECD is achieved by mutation of a threonine residue in a N-glycosylation consensus site to isoleucine. In some embodiments, hypoglycosylation of the TIM3 ECD is achieved by a T801 mutation.

In some embodiments, the TIM3 ECD or TIM3 ECD variant may be selected from the following list: SEQ ID NOS: 181; 182; 183.

In one embodiment, the fusion protein comprises a ligand-binding sequence of an extracellular domain of B- and T-lymphocyte attenuator (BTLA-ECD) or fragment thereof. In one aspect, this ligand trap (BTLA ECD) binds herpesvirus entry mediator (HVEM). In one aspect, the BTLA ECD comprises sequence that binds at least the cysteine-rich domain 1 region (CRD1) of HVEM. In another aspect the BTLA ECD sequence that binds HVEM enables HVEM to recruit the signaling molecules TNFR-associated factor (TRAF1, TRAF2, TRAF3 and/or TRAF5, activation of nuclear factor-κB (NF-κB) and/or activator protein 1 (AP1) transcription factors. In another aspect the BTLA ECD sequence promotes the co-stimulation or survival of immune cells or T-cells. In one aspect, the BTLA ECD sequence does not interfere with the interaction between HVEM and LIGHT. In another aspect, the BTLA ECD sequence binds HVEM and promotes HVEM-mediated activation of NF-κB. In another aspect, the BTLA ECD sequence lacks the C-terminal cytoplasmic domain that recruits SHP-1 or SHP-2. In this aspect, BTLA ECD binds HVEM and prevents HVEM from binding native BTLA, thereby blocking the ability of HVEM to bind native BTLA and consequent BTLA-mediated SHP1/SHP2-dependent inhibition of TCR signaling. In addition to blocking inhibitory signaling, the BTLA ECD sequence may activate HVEM-mediated activation and/or survival of T cells.

In one embodiment, the ligand trap may be a ligand-binding sequence of an extracellular domain of BTLA (BTLA ECD) or fragment thereof that is hypoglycosylated or deglycosylated (hypoglycosylated BTLA ECD or deglycosylated BTLA ECD). In some embodiments, any N-glycosylation consensus site of BTLA ECD is mutated to reduce glycosylation of BTLA ECD. In some embodiments, hypoglycosylation of the BTLA ECD is achieved by mutations at one or more of the following sites: N76, G77, T78, N95, 196, S97, N111, G112, and/or S113.

In some embodiments, the BTLA ECD or BTLA ECD variant may be selected from the following list: SEQ ID NOS: 165; 166; 167; 168

In one embodiment, the fusion protein comprises a ligand-binding sequence of an extracellular domain of SIRPa (SIRPa-ECD) or fragment thereof to bind and disable CD47. The ligand-binding N-terminal domain of SIRPa (SIRPa d1) binds CD47 through the loops at the end of the domain. CD47 possesses an unusual disulphide link between the IgSF domain and one of the loops between the transmembrane regions, which is required for optimal binding of SIRPa. In one embodiment, the fusion protein comprises a CD47 binding sequence of the extracellular region or IgSF domain of SIRPa (SIRPa ECD). In one aspect, the fusion protein comprises a CD47 binding sequence of the N-terminal domain of SIRPa (SIRPa dl). In one aspect, the SIRPa ECD may be mutated to have higher affinity for CD47. In some embodiments, the SIRPa-ECD may be selected from the following list: SEQ ID NOS: 173; 174; 175; 176

In one embodiment, the fusion protein comprises a ligand-binding sequence of an extracellular domain of Sialic Acid Binding Ig Like Lectin 10 (SIGLEC10 ECD) or fragment thereof to bind and disable CD24. SIGLEC10 is highly expressed by tumor-associated macrophages; and tumors often express high levels of CD24. Endogenous SIGLEC10 contains two ITIM domains on its cytoplasmic tail, and ligation of SIGLEC10 by CD24 results in SHP1/SHP2-mediated inhibitory signaling that prevent the macrophage from phagocytosing the CD24-expressing tumor cell. In some embodiments, the SIGLEC10 ECD may be selected from the following list: SEQ ID NOS: 172.

In some embodiments, the fusion protein comprises a ligand-binding sequence of the extracellular domain of a T cell co-stimulatory molecule or a fragment thereof. In one aspect, this ECD is capable of binding its cognate T cell co-inhibitory molecule and promote T cell activation. In some embodiments, this T cell co-stimulatory molecule is selected from OX40L, 41BBL, ICOSL, GITRL, LIGHT, CD70, CD40L, CD30L.

In some embodiments, the fusion protein may comprise a ligand-binding sequence of the extracellular domain of CD160 or a fragment thereof.

In various embodiments, the fusion proteins of the invention comprise a targeting polypeptide (TP) in addition to one or more ligand traps. The targeting polypeptide comprises a polypeptide which specifically binds a component of a tumor cell, tumor microenvironment, tumor associated growth factor or receptor, tumor associated cytokine or receptor, tumor associated T lymphocyte, T cell co-stimulatory or inhibitory molecule, immune cell, pathogen, or pathogen-associated cell.

In some embodiments, this targeting polypeptide is an antibody. In such cases, the fusion protein of the invention may be referred to as an “antibody-ligand trap”, or “ALT”, which are used interchangeably.

In one aspect, the targeting polypeptide comprises an antigen-binding domain of an immunoglobulin, antibody, bispecific or multispecific antibody, antibody fragment, single chain variable fragment (scFv), bivalent or multivalent scFv, Affimer, a ligand-binding sequence from the extracellular domain (ECD) of a receptor, or Fc-containing polypeptide. In certain aspects, the targeting polypeptide is an antibody.

In the case that the targeting polypeptide is a bispecific antibody (bsAb), it may be an obligate or non-obligate bsAb. In some embodiments, one of the targets of the bsAb is CD3.

In some embodiments, the bsAb is bivalent in a 1+1 format (i.e., one binding site for each target). In a further embodiment, the bispecific antibody may be a tandem VHH nanobody fusion, tandem scFvs (e.g., BiTE), DART, diabody, F(ab)2, or scFv-Fab fusion. In another embodiment, the bispecific antibody may comprise two or more asymmetric chains: for example, hetero heavy chains with forced knob-and-hole HL pairing, hetero heavy chains with CrossMab VH/VL swapped domains, hetero heavy chains with CrossMAB CH1/CL swapped domains, DART-Fc, LP-DART, or half-life-extended BiTE.

In other embodiments, the bsAb is trivalent in a 1+2 format (i.e., 1 binding site for one target and 2 binding sites for the other target). In a further embodiment, the bsAb is a CrossMab with 3 F(ab) regions.

In other embodiments, the bsAb is tetravalent in a 2+2 format (i.e., 2 binding sites for each target). In a further embodiment, the bsAb is a fusion of a normal IgG with 2 scFv domains, Bs4Ab, DVD-Ig, tetravalent DART-Fc, four scFv domains fused to Fc, CODV-Ig, a pair of tandem VHH nanobodies fused to Fc, or a CrossMab with 4 F(ab) regions.

Examples of bsAbs that may be used as targeting polypeptides of the fusion proteins of the invention include the following: CD3×B7-H3 (e.g., orlotamab), CD3×BCMA (e.g., AMG420, AMG701, EM801, JNJ-64007957, PF-06863135, REGN5458), CD3×CD19 (e.g., A-319, AFM11, AMG562, blinatumomab), CD3×CD20 (e.g., mosunetuzumab, plamatomab, REGN1979, CD20-TCB), CD3×CD33 (e.g., AMG330, AMG673, AMV-564, GEM333), CD3×CD38 (e.g., AMG424, GBR1342), CD3×CEA (e.g., Cibisatamab), CD3×EGFRvIII (e.g., AMG596), CD3×EpCAM (e.g., A-337, catumaxomab, removab), CD3×FLT3 (e.g., AMG427), CD3×GPC3 (e.g., ERY974), CD3×gpA33 (e.g., MGD007), CD3×GPRC5D (e.g., JNJ-64407564), CD3×HER2 (e.g., GBR1302, M802, RG6194), CD3×MUC16 (e.g., REGN4018), CD3×P-Cadherin (e.g., PF-06671008), CD3×PSMA (e.g., AMG160, MOR209, pasotuxizumab), CD3×SSTR2 (e.g., tidutamab), CD40×MSLN (e.g., ABBV-428), PD-1×ICOS (e.g., Xmab23104), or PD-L1×4-1BB (e.g., MCLA-145)

Exemplary fusion proteins of the invention comprising one or more receptor ECDs and a bispecific antibody include anti-CEACAM5/CD3 (cibisatamab) fused to BTLA on HC—e.g., SEQ ID NOs: 747, 748, 218, 219; anti-CEACAM5/CD3 (cibisatamab) fused to BTLA on LC—e.g., SEQ ID NOs: 216, 217, 749, 219; anti-CEACAM5/CD3 (cibisatamab) fused to PD1 on HC—e.g., SEQ ID NOs: 751, 752, 218, 219; anti-CEACAM5/CD3 (cibisatamab) fused to PD1 on LC—e.g., SEQ ID NOs: 216, 217, 753, 219; anti-CEACAM5/CD3 (cibisatamab) fused to SIGLEC10 on HC—e.g., SEQ ID NOs: 755, 756, 218, 219; anti-CEACAM5/CD3 (cibisatamab) fused to SIGLEC10 on LC—e.g., SEQ ID NOs: 216, 217, 757, 219; anti-CEACAM5/CD3 (cibisatamab) fused to SIRPa on HC—e.g., SEQ ID NOs: 759, 760, 218, 219; anti-CEACAM5/CD3 (cibisatamab) fused to SIRPa on LC—e.g., SEQ ID NOs: 216, 217, 761, 219; anti-CEACAM5/CD3 (cibisatamab) fused to TGFbR on HC—e.g., SEQ ID NOs: 763, 764, 218, 219; anti-CEACAM5/CD3 (cibisatamab) fused to TIM3 on HC—e.g., SEQ ID NOs: 765, 766, 218, 219; anti-CEACAM5/CD3 (cibisatamab) fused to TIM3 on LC—e.g., SEQ ID NOs: 216, 217, 767, 219; anti-CEACAM5/CD3 (cibisatamab) fused to VEGFR on HC—e.g., SEQ ID NOs: 769, 770, 218, 219; anti-CD3/PSMA (pasotuxizumab) fused to BTLA—e.g., SEQ ID NO: 729; anti-CD3/PSMA (pasotuxizumab) fused to PD1—e.g., SEQ ID NO: 733; anti-CD3/PSMA (pasotuxizumab) fused to SIGLEC10—e.g., SEQ ID NO: 737; anti-CD3/PSMA (pasotuxizumab) fused to SIRPa—e.g., SEQ ID NO: 741; anti-CD3/PSMA (pasotuxizumab) fused to TIM3—e.g., SEQ ID NO: 745.

In some embodiments, one of the targets of the bispecific antibody targeting polypeptide is CD28.

In some embodiments, this targeting polypeptide is an antibody. In such cases, the fusion protein comprising an antibody and one or more ECDs may be referred to as an “antibody-ligand trap”, or “ALT”, which are used interchangeably.

In one embodiment, the targeting polypeptidein is an immunoglobulin. As used herein, the term “immunoglobulin” includes natural or artificial mono- or polyvalent antibodies including, but not limited to, polyclonal, monoclonal, multispecific, human, humanized or chimeric antibodies, single chain antibodies, Fab fragments. F(ab′) fragments, fragments produced by a Fab expression library, anti-idiotypic (anti-Id) antibodies (including, e.g., anti-Id antibodies to antibodies of the invention), and epitope-binding fragments of any of the above. The term “antibody,” as used herein, refers to immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, i.e., molecules that contain an antigen binding site that immunospecifically binds an antigen. The immunoglobulin ion can be of any type (e.g., IgG, IgE, IgM, IgD, IgA, and IgY), class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2) or subclass of immunoglobulin molecule.

An antibody as disclosed herein includes an antibody fragment, such as, but not limited to, Fab, Fab′ and F(ab′)2, Fd, single-chain Fvs (scFv), single-chain antibodies, disulfide-linked Fvs (sdfv) and fragments including either a VL or VH domain. In one embodiment, the targeting moiety is an antibody or scFv.

An antigen-binding antibody fragment, including single-chain antibody, may include the variable region(s) alone or in combination with the entirety or a portion of the following: hinge region, CH1, CH2, and CH3 domains. An antigen-binding fragment can also include any combination of variable region(s) with a hinge region, CHI, CH2, and CH3 domains. Also includes is a Fc fragment, antigen-Fc fusion proteins, and Fc-targeting moiety. The antibody may be from any animal origin including birds and mammals. In one aspect, the antibody is, or derived from, a human, murine (e.g., mouse and rat), donkey, sheep, rabbit, goat, guinea pig, camel, horse, or chicken. Further, such antibody may be a humanized version of an antibody. The antibody may be monospecific, bispecific, trispecific, or of greater multi specificity.

The intact antibody may have one or more “effector functions” which refer to those biological activities attributable to the Fc region (a native sequence Fc region or amino acid sequence variant Fc region or any other modified Fc region) of an antibody. Examples of antibody effector functions include Clq binding; complement dependent cytotoxicity; Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g., B cell receptor (BCR); and cross-presentation of antigens by antigen presenting cells or dendritic cells. In one embodiment, the targeting antibody or Fc-containing fusion protein facilitates focused or preferential delivery of a immunomodulatory moiety to a target cell. In another aspect, a targeting antibody can induce death of the targeted cell or sensitize it to immune cell-mediated cytotoxicity. In another aspect, the Fc-fusion protein or antibody can facilitate delivery of the immunomodulatory moiety or immunogenic apoptotic material from antibody-bound tumor targets, or both, to an antigen presenting cells (APC) via interactions between their Fc and Fc receptors (on APC).

The Fc region may have one or more modifications to alter one or more of its biophysical and/or functional properties; for example, extend half-life, reduce effector function, or increase effector function. Such modifications are well-known in the art. Exemplary modifications include the “LALA” (L234A/L235A) mutation of IgG1, and the S228P mutation of IgG4.

The term “fragment” refers to any subject polypeptide having an amino acid residue sequence shorter than that of a polypeptide whose amino acid residue sequence is disclosed herein

In one embodiment, the fusion protein of the invention comprises a targeting polypeptide that specifically binds a tumor-associated molecule. In some embodiments, the targeting polypeptide binds one of the following targets: CA125, CA19-9, CD30, CEACAM5, CEACAM1, CEACAM6, DLL3, DLL4, DPEP3, EGFR, EGFRvIII, GD2, HER2, HER3, HGF, IGF1R, IL13Ra2, LIV-1, LRRC15, MUC1, PRLR, PSCA, PSMA, PTK7, SEZ6, SLAMF7, TF, cMet, claudin, mesothelin, nectin4, uPAR, GPNMB, CD79b, CD22, NaPi2b, SLTRK6, STEAP1, MUC16, CD37, GCC, AGC-16, 5T4, CD70, TROP2, CD74, CD27L, Fra, CD138, CA6.

In various embodiments, the fusion protein of the invention comprises an antibody selected from the following: 41BB: urelumab (SEQ ID NOs: 1, 2); CA125: ab1 (SEQ ID NOs: 3, 4), sofituzumab (SEQ ID NOs: 5, 6); CA19-9: MVT-5873 (SEQ ID NOs: 7, 8); CD20: rituximab (SEQ ID NOs: 9, 10); CD30: brentuximab (SEQ ID NOs: 11, 12); CD33: gemtuzumab (SEQ ID NOs: 13, 14); CD38: daratumumab (SEQ ID NOs: 15, 16); CD39: IPH5201 (SEQ ID NOs: 17, 18); CD40: ABBV-428 (SEQ ID NOs: 19, 20); CD47: 5F9 (SEQ ID NOs: 21, 22); CD73: GS1423 (SEQ ID NOs: 23, 24); CEACAM5: labetuzumab (SEQ ID NOs: 25, 26); CTLA4: ipilimumab (SEQ ID NOs: 27, 28); DLL3: rovalpituzumab (SEQ ID NOs: 29, 30); DLL4: ABT-165 (SEQ ID NOs: 31, 32); DPEP3: ab1 (SEQ ID NOs: 33, 34), ab2 (SEQ ID NOs: 35, 34); EGFR: panitumumab (SEQ ID NOs: 36, 37), necitumumab (SEQ ID NOs: 38, 39), ABBV-321 (SEQ ID NOs: 40, 41), cetuximab (SEQ ID NOs: 42, 43); EGFRvIII: ab1 (SEQ ID NOs: 44, 45), depatuxizumab (SEQ ID NOs: 46, 47); GARP: ARGX-115 (SEQ ID NOs: 48, 49); GD2: dinutuximab (SEQ ID NOs: 50, 51); HER2: pertuzumab (SEQ ID NOs: 52, 53), trastuzumab (SEQ ID NOs: 54, 55); HGF: rilotumumab (SEQ ID NOs: 56, 57); ICOS: GSK3359609 (SEQ ID NOs: 58, 59); IL13Ra2: ab1 (SEQ ID NOs: 60, 61); IL17R: brodalumab (SEQ ID NOs: 62, 63); ILla: 3D12r16 (SEQ ID NOs: 64, 65); ILlb: E26.35 (SEQ ID NOs: 66, 67), canakinumab (SEQ ID NOs: 68, 69); IL23: brazikumab (SEQ ID NOs: 70, 71), guselkumab (SEQ ID NOs: 72, 73), risankizumab (SEQ ID NOs: 74, 75), tildrakizumab (SEQ ID NOs: 76, 77); IL6R: tocilizumab (SEQ ID NOs: 78, 79); LAP: 7H4 (SEQ ID NOs: 80, 81); LIV-1: ladiratuzumab (SEQ ID NOs: 82, 83); LRRC15: ABBV-085-huAD208.4.1 (SEQ ID NOs: 84, 85), ABBV-085-huM25 (SEQ ID NOs: 86, 87); MUC1: clivatuzumab (SEQ ID NOs: 88, 89); OX40: ABBV-368-Hu3726 (SEQ ID NOs: 90, 91), ABBV-368-Hu3739 (SEQ ID NOs: 92, 93), ABBV-368-Hu3741 (SEQ ID NOs: 94, 95), GSK3174998 (SEQ ID NOs: 96, 97); PD1: spartalizumab (SEQ ID NOs: 98, 99), pembrolizumab (SEQ ID NOs: 100, 101), ABBV-181 (SEQ ID NOs: 102, 103), nivolumab (SEQ ID NOs: 104, 105); PDGF: ab1 (SEQ ID NOs: 106, 107); PDL1: atezolizumab (SEQ ID NOs: 108, 109), avelumab (SEQ ID NOs: 110, 111), durvalumab (SEQ ID NOs: 112, 113); PRLR: ab1 (SEQ ID NOs: 114, 115); PSCA: ab1 (SEQ ID NOs: 116, 117); PSMA: ab2 (SEQ ID NOs: 118, 119), ab1 (SEQ ID NOs: 120, 121); PTK7: hSC6.24 (SEQ ID NOs: 122, 123); SEZ6: hSC17.200 (SEQ ID NOs: 124, 125); SLAMF7: elotuzumab (SEQ ID NOs: 126, 127); TF: tisotumab (SEQ ID NOs: 128, 129); TGFb: XOMA-089 (SEQ ID NOs: 130, 131), fresolimumab (SEQ ID NOs: 132, 133); TGFbRII: LY3022859 (SEQ ID NOs: 134, 135); TIGIT: etigilimab (SEQ ID NOs: 136, 137), tiragolumab (SEQ ID NOs: 138, 139); TIM3: M6903 (SEQ ID NOs: 140, 141); VEGF: ranibizumab (SEQ ID NOs: 142, 143), bevacizumab (SEQ ID NOs: 144, 32), ABT-165 (SEQ ID NOs: 145, 146), ab1 (SEQ ID NOs: 144, 32); VEGFR: ramucirumab (SEQ ID NOs: 147, 148); VISTA: onvatilimab (SEQ ID NOs: 149, 150); cMet: telisotuzumab (SEQ ID NOs: 151, 152); claudin: hSC27.1 (SEQ ID NOs: 153, 154); gp120: B12 (SEQ ID NOs: 155, 156); mesothelin: ABBV-428 (SEQ ID NOs: 157, 158); nectin4: enfortumab (SEQ ID NOs: 159, 160); uPAR: ab1 (SEQ ID NOs: 161, 162), ab2 (SEQ ID NOs: 163, 164).

In one embodiment, the targeting polypeptide specifically binds human epidermal growth factor receptor 2 (HER2; ErbB2). HER2 is overexpressed in many human cancers, including breast cancer and gastric cancer. In HER2-overexpressing cells, excess levels of HER2 expression can result in spontaneous and constitutive ligand-independent dimerization with subsequent activation of the cytoplasmic kinase region. HER2 can additionally heterodimerize with HER3 and EGFR. Each of these interactions leads to kinase signaling that stimulates phosphorylation and downstream signaling, primarily through the PI3K-Akt-mTOR and Ras-Raf-MEK-Erk pathways. Activation of these pathways promotes proliferation, evasion of apoptosis, angiogenesis, and invasion, leading to tumor growth and progression. anti-HER2 antibody (trastuzumab) inhibits homodimerization and autophosphorylation of HER2, as well as heterodimerization of HER2 with EGFR. anti-HER2 antibody (pertuzumab) interrupts the HER2/HER3 interaction or downstream signaling of the HER2/HER3 heterodimer in complex with HER3 ligand (heregulin). In some embodiments, the antibody of the ALT that binds HER2 is selected from one of the following: pertuzumab (SEQ ID NOS. 52, 53); trastuzumab (SEQ ID NOS. 54, 55). In one aspect, the HER2 targeted antibody is conjugated to a cytotoxic agent (anti-HER2-ADC), such as ado-trastuzumab (Trastuzumab-DM1). In various embodiments, the fusion protein of the invention comprises an antibody that targets and inhibits HER2 fused to one or more receptor ECDs.

In one embodiment, the targeting polypeptide specifically binds epidermal growth factor receptor (EGFR). In epithelial tumors, the epidermal growth factor receptor (EGFR) controls key signaling pathways responsible for growth, proliferation, migration, and survival of tumor cells. The epidermal growth factor receptor variant III (EGFRvIII) is the most common EGFR mutation that occurs frequently in high-grade gliomas especially glioblastoma multiforme (GBM). EGFRvIII arises from the deletion of exon 2-7 that leads to the formation of the constitutively activated mutant receptor incapable of binding any known ligand. EGFRvIII-expressing cells are resistant to EGFR inhibitors, and EGFRvIII expression in tumors is often correlates with poor prognosis. The presence of the unique glycine site in EGFRvIII provides an option to develop EGFRvIII-specific monoclonal antibodies. Examples of antibodies targeting EGFRvIII include depatuxizumab. Examples of EGFR antibodies include cetuximab, panitumumab, and necitumumab. In some embodiments, the antibody of the ALT that binds EGFR is selected from one of the following: panitumumab (SEQ ID NOS. 36, 37); necitumumab (SEQ ID NOS. 38, 39); ABBV-321 (SEQ ID NOS. 40, 41); cetuximab (SEQ ID NOS. 42, 43). In various embodiments, the fusion protein of the invention comprises a polypeptide that targets and inhibits EGFR or EGFRvIII fused to one or more receptor ECDs.

In one embodiment, the targeting polypeptide specifically binds Prostate-specifc membrane antigen (PSMA). PSMA is a non-soluble type 2 integral membrane protein. It is weakly expressed in normal prostate tissue but strongly upregulated in prostate cancer. It is also expressed in the neovasculature of numerous solid malignancies. PSMA overexpression is associated with higher Prostate Cancer grade and androgen deprivation, further increasing in metastatic disease and castration resistant Prostate Cancer. In one embodiment, the ALT specifically binds an epitope of PSMA necessary for its functional activity, such as PI3K activation. In some embodiments, the antibody of the ALT that binds PSMA is selected from one of the following: ab2 (SEQ ID NOS. 118, 119); ab1 (SEQ ID NOS. 120, 121). In one aspect, the PSMA targeted antibody is conjugated to a cytotoxic agent (anti-PSMA-ADC). In various embodiments, the fusion protein of the invention comprises a polypeptide that targets and binds PSMA fused to one or more receptor ECDs.

In one embodiment, the targeting polypeptide specifically binds the urokinase-type plasminogen activator receptor (uPAR). uPAR is a GPI-anchored cell membrane receptor, composed by three homologous domains (DI, DII, DIII). Its main function is focusing of urokinase (uPA) proteolytic activity, responsible for degradation of extracellular matrix (ECM) components, on the cell surface. When uPA binds uPAR, it consequently converts plasminogen to active plasmin, which activates several proteases related to the degradation of extracellular matrix proteins and basal membranes, thereby facilitating cancer cell invasion and metastasis. uPAR expression is increased in many human cancers and correlates with a poor prognosis and early invasion and metastasis. uPAR is an adhesion receptor, as it binds vitronectin (VN), an abundant component of provisional extracellular matrix (ECM). This direct interaction between uPAR and VN is critical for triggering changes in cell morphology, migration and signaling and is an important requirement for the induction of epithelial mesenchymal transition (EMT). In some embodiments, the antibody of the ALT specifically inhibits the uPA/uPAR interaction. In other embodiments, the ALT specifically inhibits the vitronectin/uPAR interaction. In one aspect the antibody binds a sequence or domain of uPAR that remains on the cell surface following cleavage. In some embodiments, the antibody of the ALT that binds uPAR is selected from one of the following: ab1 (SEQ ID NOS. 161, 162); ab2 (SEQ ID NOS. 163, 164). In one aspect, the uPAR targeted antibody is conjugated to a cytotoxic agent (anti-uPAR-ADC). In various embodiments, the fusion protein of the invention comprises a polypeptide that targets and binds uPAR, fused to one or more receptor ECDs.

In some embodiments, the targeting polypeptide binds an antigen overexpressed by a hematologic malignancy. In some embodiments, the targeting polypeptide binds an antigen overexpressed by multiple myeloma. In some embodiments, the targeting polypeptide binds CD38, SLAMF7, or BCMA. In some embodiments, the targeting polypeptide is an antibody selected from the following list: MEDI2228; CC-99712; belantamab; Gemtuzumab (anti-CD33 mAb). In some embodiments, the targeting polypeptide binds an antigen overexpressed by Non-Hodgkin's B cell lymphomas. In some embodiments, the antibody binds CD20. In some embodiments, the targeting polypeptide binds rituximab (chimeric murine/human anti-CD20 mAb); Obinutuzumab (anti-CD20 mAb); Ofatumumab (anti-CD20 mAb); Tositumumab-I131 (anti-CD20 mAb); Ibritumomab tiuxetan (anti-CD20 mAb). In some embodiments, the targeting polypeptide binds CD19. In some embodiments, the targeting polypeptide binds an antigen overexpressed by Hodgkin's lymphomas. In some embodiments, the antibody binds CD30, or CD22. In some embodiments, the targeting polypeptide binds an antigen overexpressed by leukemia. In some embodiments, the ALT binds CD33.

T cell activation begins with the recognition of an antigenic peptide in the context of a major histocompatibility complex (MHC) on an antigen-presenting cell by the T cell receptor (TCR). The process of T cell activation is mediated by a number of signaling proteins through inducible phosphorylation, enzyme activation and protein-protein and protein-lipid interactions. T cells require two signals to become fully activated. A first signal, which is antigen-specific, is provided through the T cell receptor (TCR) which interacts with peptide-MHC molecules on the membrane of antigen presenting cells (APC). A second signal, the co-stimulatory signal, is antigen nonspecific and is provided by the interaction between co-stimulatory molecules expressed on the membrane of APC and the T cell. T cell co-stimulation is necessary for T cell proliferation, differentiation and survival. Activation of T cells without co-stimulation may lead to T cell anergy, T cell deletion or the development of immune tolerance.

The best characterized T cell co-stimulatory molecules expressed by T cells is CD28 which interacts with CD80 (B7.1) and CD86 (B7.2) on the membrane of APC. Other costimulatory receptors expressed by T cells include 4-1BB (receptor for 4-1BB ligand), ICOS (Inducible Costimulator) (receptor for ICOS-L), OX40 (receptor for OX40 ligand), GITR (receptor for GITR ligand), CD27 (interacts with CD70), CD40L/CD40, HVEM (interacts with LIGHT), CD226 (interacts with CD155).

The activation signals are modulated by a family of receptors termed, T cell co-inhibitory receptors that include CTLA-4, PD-1, LAG-3, TIM-3, CEACAM-1, TIGIT, CD96, BTLA, CD160, VISTA, VSIG8, LAIR. Co-inhibitory receptors modulate signaling by utilizing mechanisms such as ectodomain competition with counter receptors and by the use of intracellular mediators such as protein phosphatases. Co-inhibitory receptors can act as threshold-setters, modulators, checkpoints and feedback mechanisms that can fine tune the quality and magnitude of the T cell immune response.

Receptors that are inhibitory to T cell function are termed T cell co-inhibitory receptors. Inhibitory receptors attenuate and counterbalance activation signals initiated by stimulatory receptors. The subsequent outcomes on T cell function can range from temporary inhibition to permanent inactivation and cell death. TCR signaling can be controlled by various mechanisms that differ in their time of action and/or target molecule. Negative regulatory mechanisms are in place to act before T cell activation to maintain its quiescent state.

The majority of T cell co-inhibitory receptors belong to the immunoglobulin (Ig) superfamily. One mechanism involves the sequestration of the ligands for co-stimulatory receptors, depriving the T cell from receiving activation signals necessary for complete activation. The second mechanism involves the recruitment of intracellular phosphatases by an immunoreceptor tyrosine-based inhibition motif (ITIM) and/or an immunoreceptor tyrosine-based switch motif (ITSM) that make up the cytoplasmic tail of certain inhibitory receptors, which dephosphorylate signalling molecules downstream of the TCR and co-stimulatory pathways, leading to a quantitative reduction in activation-induced gene expression. The third mechanism involves the upregulation (or downregulation) of genes that code for proteins involved in the inhibition of immune functions. A co-inhibitory receptor could use a combination of the above and possibly other yet to be discovered mechanisms to regulate T cell signaling.

T cell co-inhibitory receptors are transmembrane glycoproteins that transmit dominant negative signals mainly via intracellular phosphatases that bind to phosphorylated tyrosine residues in the cytoplasmic domain. T cell co-inhibitory receptors can act as safety mechanisms and threshold setters to prevent uncontrolled detrimental extremes of reactivity by counteracting the stimulatory signals.

In one embodiment, the fusion protein of the invention comprises a targeting polypeptide that specifically binds a T cell co-inhibitory receptor (TCIR), a T cell co-inhibitory receptor ligand (TCIR ligand), a T-cell co-inhibitory molecule, or a T cell co-stimulatory molecule. In an additional aspect, the antibody is an antagonist of a TCIR, TCIR ligand, or T cell co-inhibitory molecule. In an additional aspect, the targeting moiety polypeptide specifically binds one or more of the following molecules: Cytotoxic T lymphocyte associated antigen-4 (CTLA-4, CD152), Programmed Death-1 protein (PD-1), Programmed death ligand-1 (PD-L1), Programmed death ligand (PD-L2), B7-H3 (CD276), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), Carcinoembryonic antigen-related cell adhesion molecule (CEACAM), V domain Ig suppressor of T cell activation (VISTA), V-set and immunoglobulin domain containing 8 (VSIG8), B and T lymphocyte attenuator (BTLA), Herpesvirus Entry Mediator (HVEM), CD160, T cell Ig and ITIM domain (TIGIT), CD226, CD96, Lymphocyte activation gene-3 (LAG-3).

In another aspect, the targeting polypeptide is an agonist of a T cell co-stimulatory molecule. In one aspect, the targeting polypeptide is an antibody that binds a T cell co-stimulatory molecule as an agonist. In another aspect, the targeting polypeptide is the extracellular domain of a native agonist ligand of a T cell co-stimulatory molecule. In an additional aspect, the targeting polypeptide specifically binds one of the following molecules: 4-1BB (CD137), Inducible T-Cell Costimulator (ICOS), OX-40 (CD134), glucocorticoid-induced TNFR-related protein (GITR), CD40, DNAM, CD30, or CD27. In various embodiments, an ALT of the invention comprises an antibody that binds a T cell co-inhibitory molecule or a T cell co-stimulatory molecule, wherein the said antibody is fused with one or more receptor ECDs.

In one embodiment, the fusion protein of the invention comprises a targeting polypeptide that specifically binds a “don't eat me” or anti-phagocytic ligand or receptor that inhibits the function of macrophages, dendritic cells, or other innate immune cells. Anti-phagocytic ligands expressed by cells bind their cognate receptor on a macrophage, dendritic cell, or other innate immune cell to inhibit phagocytosis. Tumor cells take advantage of this anti-phagocytic mechanism and overexpress “don't eat me” ligands in order to inhibit innate immune cell antitumor activity. In some embodiments, the targeting polypeptide binds CD47, SIRPa, CD31, CD24, SIGLEC10, or LILRB1.

In another aspect, the targeting polypeptide binds and disables the interaction of CD47 and SIRPa. CD47 is a “don't eat me signal” expressed by tumor cells that binds SIRPa on macrophages and induces SHP1/SHP2-mediated inhibition of macrophage phagocytosis. In various embodiments, an ALT of the invention comprises an antibody that binds and disables CD47, wherein the said antibody is fused with one or more receptor ECDs. In another aspect, the targeting polypeptide binds and disables a different “don't eat me” interaction—for example, LILRB1/MHC, SIGLEC10/CD24, or CD31/CD31. In various embodiments, the targeting polypeptide is an antibody that binds one of these targets.

In one embodiment, the targeting polypeptide comprises a polypeptide or antibody that specifically binds Programmed death-1 (PD-1; CD279) or Programmed death-1 ligands [PD-L1 (B7-H1); PD-L2 (B7-H4)]. Tumor cells express PD-1 ligands which inhibit T cell effector function and induce T cell exhaustion/apoptosis via engagement of PD-1. In one embodiment, the ALT comprises an antibody that specifically binds PD-1 and disrupts its interaction with PD-L1 or PD-L2. In one embodiment, the ALT comprises an antibody that specifically binds PD-L1 and disrupts its interaction with either PD-1 or B7: atezolizumab (SEQ ID NOS. 108, 109); avelumab (SEQ ID NOS. 110, 111); durvalumab (SEQ ID NOS. 112, 113). In another embodiment, the ALT comprises an antibody that specifically binds PD-1: spartalizumab (SEQ ID NOS. 98, 99); pembrolizumab (SEQ ID NOS. 100, 101); ABBV-181 (SEQ ID NOS. 102, 103); nivolumab (SEQ ID NOS. 104, 105).

In some embodiments, the drug conjugate is selected from: mitotic inhibitors, antitumor antibiotics, immunomodulating agents, vectors for gene therapy, alkylating agents, antiangiogenic agents, antimetabolites, boron-containing agents, chemoprotective agents, hormones, antihormone agents, corticosteroids, photoactive therapeutic agents, oligonucleotides, radionuclide agents, topoisomerase inhibitors, tyrosine kinase inhibitors, and radiosensitizers.

In one embodiment, the fusion protein comprising a tumor-targeted antibody and one or more ECDs is expressed using recombinant methods well-known in the art, and then a conjugation procedure well-known in the art is applied to attach the cytotoxic agent to the fusion protein. In some embodiments, the cytotoxic agent may be conjugated to the fusion protein using cysteine-specific conjugation methods well-known in the art. In other embodiments, the cytotoxic agent may be conjugated to the fusion protein using lysine-specific conjugation methods well-known in the art. In other embodiments, the cytotoxic agent may be conjugated to the fusion protein in a site-specific manner well-known in the art. In some embodiments, this may be achieved via HIPS ligation (Hydrazinyl-Iso-Pictet-Spengler (HIPS) ligation to formylglycine), trapped Knoevenagel condensation, or tandem Knoevenagel condensation-Michael Addition (TKM) ligation.

In various embodiments, the fusion proteins of the invention counteract VEGF in the tumor microenvironment. In some embodiments, the fusion proteins comprise a ligand-binding sequence of an extracellular domain of VEGFR (e.g., VEGFR ECD).

In one aspect, the fusion proteins of the invention comprise an antibody that targets a tumor antigen or tumor-associated antigen expressed in the TME, wherein said antibody is fused to a VEGF-binding sequence from one or more extracellular domains of VEGFR (e.g. VEGFR1ECD and/or VEGFR2ECD). In one example, the ALT comprises vascular endothelial growth factor (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2. The VEGFR ECD fused to the ALT localizes to the TME, where it serves as a decoy receptor to bind and disable VEGF (e.g VEGF-A, VEGF-B). In another aspect an ALT comprising a fused ligand-binding sequence of VEGFR ECD is additionally fused to a different receptor ECD that captures and disables its cognate ligands (e.g. TGFbRII ECD, PD-1ECD, TIM-3ECD, SIRPa ECD, BTLA ECD). In one aspect, the VEGFR ECD is fused to the C-terminus of the heavy chain of the targeting antibody, and another different receptor ECD is fused to the C-terminus of the light chain.

In other embodiments, the fusion proteins of the invention comprise a targeting polypeptide that binds VEGF or VEGFR fused to one or more receptor ECDs. These receptor ECDs are preferably selected from the following: PD1 ECD, TIM-3 ECD, TGFbRII ECD, BTLA ECD, SIRPa ECD, SIGLEC10 ECD. In some embodiments, the targeting polypeptide that binds VEGF or VEGFR is an antibody.

In another aspect, the ALT is a polypeptide comprising an antibody that targets VEGF or VEGFR, wherein said antibody is fused to a ligand-binding sequence of an extracellular domain of a receptor. In one example, the ALT comprises an antibody that targets either VEGF or VEGFR, wherein said antibody is fused to a TGFb-binding sequence of an extracellular domain of the TGFbR (e.g. TGFbRII ECD). In another example, the ALT comprises an antibody that targets either VEGF or VEGFR, wherein said antibody is fused to a PD-1 ligand-binding sequence of an extracellular domain of PD-1 (PD-1ECD). In another example, the ALT comprises an antibody that targets either VEGF or VEGFR, wherein said antibody is fused to a TIM-3 ligand-binding sequence of an extracellular domain of TIM-3 (TIM-3ECD). In another example, the ALT comprises an antibody that targets either VEGF or VEGFR, wherein said antibody is fused to a CD47-binding sequence of an extracellular domain of SIRPa (e.g. SIRPa ECD). In another example, the ALT comprises an antibody that targets either VEGF or VEGFR, wherein said antibody is fused to a HVEM-binding sequence of an extracellular domain of BTLA (e.g. BTLA ECD). In another aspect an ALT comprises an antibody that targets either VEGF or VEGFR, wherein said antibody is fused to a ligand-binding sequence of a specific receptor ECD (receptor ECD-1), and additionally fused to a ligand-binding sequence of another different receptor ECD (receptor ECD-2). In various examples, receptor ECD-1 and receptor ECD-2 may be selected from a group comprising TGFbRII ECD, PD-1ECD, TIM-3ECD, BTLA ECD and SIRPa ECD. In one aspect, the receptor ECD-1 sequence is fused to the C-terminus of the heavy chain of the targeting antibody, and another different receptor ECD-2 sequence is fused to the C-terminus of the light chain. In one aspect, the receptor ECD (that is fused to a VEGF or VEGFR1 targeting antibody) binds to a cognate ligand expressed in the TME, thereby localizing the ALT and consequent VEGF/VEGFR blockade to the TME. In one example, a PD-1ECD binds PD-L1 or PD-L2 expressed on tumor cells or the TME. In another example, a TIM-3ECD binds CEACAM-1 or CEACAM-5 or CEACAM-6 expressed on tumor cells or the TME. In another example, a SIRPa ECD binds CD47 expressed on tumor cells or the TME. In another example, a BTLA ECD binds HVEM expressed on tumor cells or the TME.

Examples of such ALTs that capture and disable VEGF or block VEGFR signaling in the TME include, but are not limited to the following: ALTs comprising an antibody fused to VEGFR ECD (with or without another receptor ECD fused to the same antibody); ALTs where the antibody binds VEGF, fused to one or more Receptor ECD(s); ALTs where the antibody binds VEGFR, fused to one or more Receptor ECD(s)

In one embodiment, the fusion proteins of the invention may comprise a ligand-binding sequence of an extracellular domain of Vascular endothelial growth factor receptor (VEGFR1 and/or VEGFR2) to bind and disable VEGF.

In some embodiments, fusion proteins of the invention comprise VEGFR ECD and a polypeptide that inhibits CD47/SIRPa. Although CD47 targeted antibodies can promote antitumor immune responses by inhibiting the interaction of CD47 with SIRPa, its antitumor efficacy may be limited by disruption of TSP-1/CD47-dependent inhibition of VEGF and angiogenesis. In one embodiment, the ALT is a polypeptide comprising an antibody that targets CD47, wherein said antibody is fused to a VEGFR ECD. In this aspect, the ALT promotes antitumor immunity by disrupting the interaction of CD47 with SIRPa, while simultaneously counteracting VEGF-mediated tumor angiogenesis. In another aspect, the ALT comprises a VEGF-binding sequence from VEGFR ECD and a CD47-binding sequence from one or more extracellular domains of SIRPa (SIRPa ECD).

In some embodiments, the fusion protein comprises VEGFR ECD and a polypeptide that inhibits the interaction between CD47 and SIRPa. In one embodiment, this fusion protein comprises VEGFR ECD and a polypeptide that binds CD47. In one embodiment, this fusion protein is anti-CD47 mAb fused to VEGFR ECD (anti-CD47-VEGFR (e.g., SEQ ID NOs: 392, 22)). In another embodiment, this fusion protein comprises SIRPa ECD and VEGFR ECD. In one embodiment, this fusion protein is SIRPa-Fc-VEGFR (e.g., SEQ ID NO: 552) or VEGFR-Fc-SIRPa (e.g., SEQ ID NO: 568).

In a further aspect, the fusion protein comprises VEGFR ECD, a polypeptide that inhibits the interaction between CD47 and SIRPa, and another polypeptide that inhibits a T cell co-inhibitory molecule. In some embodiments, this fusion protein comprises anti-CD47 mAb with VEGFR ECD fused to the heavy chain; and a T cell co-inhibitory molecule ECD fused to the light chain. In a particular embodiment, this fusion protein is anti-CD47-VEGFR-PD1 (e.g., SEQ ID NOs: 392, 384).

In another aspect, the fusion protein comprises VEGFR ECD, SIRPa ECD, and an antibody with a heavy chain and light chain. In a preferred embodiment, the VEGFR ECD is fused to the heavy chain of the antibody and the SIRPa ECD is fused to the light chain of the antibody. In some embodiments, the antibody of said fusion protein binds a T cell co-inhibitory molecule as an antagonist. Exemplary embodiments of such fusion proteins include anti-CTLA4-VEGFR-SIRPa (e.g., SEQ ID NOs: 446, 438), anti-PD1-VEGFR-SIRPa (e.g., SEQ ID NOs: 458, 450), and anti-PDL1-VEGFR-SIRPa (e.g., SEQ ID NOs: 468, 461). In other embodiments, the antibody of said fusion protein binds a T cell co-stimulatory molecule as an agonist. Exemplary embodiments of this fusion protein include anti-OX40-VEGFR-SIRPa (e.g., SEQ ID NOs: 516, 508), anti-41BB-VEGFR-SIRPa (e.g., SEQ ID NOs: 504, 496), and anti-CD40-VEGFR-SIRPa. In other embodiments, the antibody of said fusion protein is a tumor-targeted antibody. In some embodiments, this tumor targeted-antibody binds a tumor growth factor or growth factor receptor. In other embodiments, this tumor targeted antibody binds a tumor cell surface molecule. Exemplary embodiments of this fusion protein include anti-EGFR-VEGFR-SIRPa (e.g., SEQ ID NOs: 231, 223), anti-HER2-VEGFR-SIRPa (e.g., SEQ ID NOs: 255, 247), anti-EGFRvIII-VEGFR-SIRPa (e.g., SEQ ID NOs: 243, 235), anti-uPAR-VEGFR-SIRPa, and anti-PSMA-VEGFR-SIRPa.

In other embodiments, the antibody of said fusion protein binds a member of the TGFb pathway. In some embodiments, this antibody binds TGFb, TGFbR, or GARP. Exemplary embodiments of this fusion protein include anti-TGFb-VEGFR-SIRPa (e.g., SEQ ID NOs: 403, 396), anti-TGFbR-VEGFR-SIRPa, and anti-GARP-VEGFR-SIRPa.

In some embodiments, the fusion protein comprises VEGFR ECD and a polypeptide that inhibits a T cell co-inhibitory molecule. In specific embodiments, the fusion protein comprises VEGFR ECD and an antibody that binds and disables a T cell co-inhibitory molecule.

In some embodiments, the fusion protein comprises VEGFR ECD and a polypeptide that inhibits the interaction of TIGIT or PVRIG with PVRL2 or PVR. In some embodiments, this fusion protein comprises an antibody that binds TIGIT or PVRIG fused to VEGFR ECD. Exemplary embodiments of this fusion protein include anti-TIGIT-VEGFR (e.g., SEQ ID NOs: 480, 139) and anti-PVRIG-VEGFR.

In some embodiments, the fusion protein comprises VEGFR ECD and a polypeptide that inhibits the interaction of VISTA and VSIG8. In some embodiments, this fusion protein comprises an antibody that binds VISTA or VSIG8 fused to VEGFR ECD. Exemplary embodiments of this fusion protein include anti-VISTA-VEGFR and anti-VSIG8-VEGFR.

In some embodiments, the fusion protein comprises VEGFR ECD and a polypeptide that inhibits the interaction of PD-1 and PD-L1. In some embodiments, this fusion protein comprises an antibody that binds PD-1 or PD-L1 fused to VEGFR ECD. Exemplary embodiments of this fusion protein include anti-PD1-VEGFR (e.g., SEQ ID NOs: 458, 101) and anti-PDLL-VEGFR (e.g., SEQ ID NOs: 468, 109).

In some embodiments, the fusion protein comprises VEGFR ECD and a polypeptide that inhibits CTLA-4. In some embodiments, this fusion protein comprises an antibody that binds CTLA-4 fused to VEGFR ECD. Exemplary embodiments of this fusion protein include anti-CTLA4-VEGFR (e.g., SEQ ID NOs: 446, 28).

In some embodiments, the fusion protein comprises VEGFR ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and an additional receptor ECD. In one aspect, the VEGFR ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the VEGFR ECD is fused to the light chain and the additional receptor ECD is fused to the heavy chain.

In some embodiments, the fusion protein comprises VEGFR ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and PD1 ECD. Exemplary embodiments of this fusion protein include anti-CTLA4-VEGFR-PD1 (e.g., SEQ ID NOs: 446, 436); anti-PD1-VEGFR-PD1 (e.g., SEQ ID NOs: 458, 448); anti-TIGIT-VEGFR-PD1 (e.g., SEQ ID NOs: 480, 470); anti-TIM3-VEGFR-PD1 (e.g., SEQ ID NOs: 492, 482).

In other embodiments, the fusion protein comprises VEGFR ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and SIRPa ECD. Exemplary embodiments of this fusion protein include anti-PDLL-VEGFR-SIRPa (e.g., SEQ ID NOs: 468, 461); anti-PD1-VEGFR-SIRPa (e.g., SEQ ID NOs: 458, 450); anti-CTLA4-VEGFR-SIRPa (e.g., SEQ ID NOs: 446, 438); anti-TIGIT-VEGFR-SIRPa (e.g., SEQ ID NOs: 480, 472); anti-TIM3-VEGFR-SIRPa (e.g., SEQ ID NOs: 492, 484).

In other embodiments, the fusion protein comprises VEGFR ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and SIGLEC10 ECD. Exemplary embodiments of this fusion protein include anti-TIGIT-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 480, 471); anti-CTLA4-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 446, 437); anti-PD1-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 458, 449); anti-TIM3-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 492, 483); anti-PDL1-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 468, 460).

In some embodiments, the fusion protein comprises an antibody that binds a T cell co-stimulatory molecule fused to VEGFR. This antibody is preferably an agonist of the T cell co-stimulatory molecule. In some embodiments, this fusion protein is selected from: anti-OX40-VEGFR (e.g., SEQ ID NOs: 516, 97); anti-41BB-VEGFR (e.g., SEQ ID NOs: 504, 2); anti-ICOS-VEGFR (e.g., SEQ ID NOs: 528, 59).

In a further aspect, the fusion protein comprises an antibody that binds a T cell-costimulatory molecule, VEGFR ECD, and an additional receptor ECD. In a preferred embodiment, the VEGFR ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-41BB-VEGFR-PD1 (e.g., SEQ ID NOs: 504, 494); anti-OX40-VEGFR-PD1 (e.g., SEQ ID NOs: 516, 506); anti-ICOS-VEGFR-PD1 (e.g., SEQ ID NOs: 528, 518). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-41BB-VEGFR-SIRPa (e.g., SEQ ID NOs: 504, 496); anti-ICOS-VEGFR-SIRPa (e.g., SEQ ID NOs: 528, 520); anti-OX40-VEGFR-SIRPa (e.g., SEQ ID NOs: 516, 508). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-OX40-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 516, 507); anti-41BB-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 504, 495); anti-ICOS-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 528, 519).

In some embodiments, the fusion protein comprises an antibody, VEGFR ECD, and the ECD of a T cell co-stimulatory molecule. In a preferred embodiment, the VEGFR ECD is fused to heavy chain and the ECD of a T cell co-stimulatory molecule fused to light chain. In some embodiments, the fusion protein comprises VEGFR ECD and one of the following: OX40L, 41BBL, ICOSL. Exemplary embodiments of these fusion proteins include the following: VEGFR-Fc-41BBL (e.g., SEQ ID NO: 631); VEGFR-Fc-ICOSL (e.g., SEQ ID NO: 641); VEGFR-Fc-OX40L (e.g., SEQ ID NO: 645) and 41BBL-Fc-VEGFR (e.g., SEQ ID NO: 632); OX40L-Fc-VEGFR (e.g., SEQ ID NO: 646); ICOSL-Fc-VEGFR (e.g., SEQ ID NO: 642).

In one embodiment, the fusion protein comprises VEGFR ECD and a polypeptide that binds an ectonucleotidase. In a preferred embodiment, the ectonucleotidase is either CD39 or CD73. In some embodiments, the fusion protein is an antibody that binds CD39 or CD73 fused to VEGFR ECD; for example: anti-CD39-VEGFR (e.g., SEQ ID NOs: 434, 18) or anti-CD73-VEGFR (e.g., SEQ ID NOs: 427, 24).

In some embodiments, the fusion protein comprises VEGFR ECD, an antibody that binds CD39 or CD73, and an additional receptor ECD. In a preferred embodiment, the VEGFR ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. In some embodiments, the fusion protein is selected from the following: anti-CD73-VEGFR-SIRPa (e.g., SEQ ID NOs: 427, 419); anti-CD73-VEGFR-PD1 (e.g., SEQ ID NOs: 427, 417).

In some embodiments, the fusion protein comprises a tumor-targeted antibody and VEGFR ECD. In some embodiments, this tumor targeted-antibody binds a tumor growth factor or growth factor receptor. In other embodiments, this tumor targeted antibody binds a tumor cell surface molecule. In some embodiments, this fusion protein is selected from the following: anti-EGFR-VEGFR (e.g., SEQ ID NOs: 231, 43), anti-HER2-VEGFR (e.g., SEQ ID NOs: 255, 55), anti-EGFRvIII-VEGFR (e.g., SEQ ID NOs: 243, 47), anti-uPAR-VEGFR (e.g., SEQ ID NOs: 274, 162), anti-PSMA-VEGFR (e.g., SEQ ID NOs: 281, 121), anti-nectin-4-VEGFR.

In a further embodiment, the fusion protein comprises a tumor-targeted antibody, VEGFR ECD, and an additional receptor ECD. In a preferred embodiment, the VEGFR ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-EGFRvIII-VEGFR-PD1 (e.g., SEQ ID NOs: 243, 233); anti-HER2-VEGFR-PD1 (e.g., SEQ ID NOs: 255, 245); anti-EGFR-VEGFR-PD1 (e.g., SEQ ID NOs: 231, 221); anti-nectin4-VEGFR-PD1 (e.g., SEQ ID NOs: 267, 257). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-EGFR-VEGFR-SIRPa (e.g., SEQ ID NOs: 231, 223); anti-nectin4-VEGFR-SIRPa (e.g., SEQ ID NOs: 267, 259); anti-HER2-VEGFR-SIRPa (e.g., SEQ ID NOs: 255, 247); anti-EGFRvIII-VEGFR-SIRPa (e.g., SEQ ID NOs: 243, 235). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-EGFR-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 231, 222); anti-EGFRvIII-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 243, 234); anti-HER2-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 255, 246); anti-nectin4-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 267, 258).

In some embodiments, the fusion protein comprises an antibody that binds IL-17 or IL-17R and VEGFR ECD. In some embodiments, this fusion protein is selected from the following: anti-IL17-VEGFR, anti-IL17R-VEGFR (e.g., SEQ ID NOs: 336, 63).

In a further embodiment, the fusion protein comprises an antibody that binds IL-17 or IL-17R, VEGFR ECD, and an additional receptor ECD. In one embodiment, VEGFR ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, VEGFR ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-IL17R-VEGFR-PD1 (e.g., SEQ ID NOs: 336, 326). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-IL17R-VEGFR-SIRPa (e.g., SEQ ID NOs: 336, 328). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL17R-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 336, 327).

In some embodiments, the fusion protein comprises an antibody that binds IL-23 or IL-23R and VEGFR ECD. If the antibody binds IL-23, it is preferred that the antibody bind the p19 subunit of IL-23 that is not shared with IL-12. In some embodiments, this fusion protein is selected from the following: anti-IL23-VEGFR (e.g., SEQ ID NOs: 348, 75), anti-IL23R-VEGFR.

In a further embodiment, the fusion protein comprises an antibody that binds IL-23 or IL-23R, VEGFR ECD, and an additional receptor ECD. In one embodiment, VEGFR ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, VEGFR ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-IL23-VEGFR-PD1 (e.g., SEQ ID NOs: 348, 338). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-IL23-VEGFR-SIRPa (e.g., SEQ ID NOs: 348, 340). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL23-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 348, 339).

In some embodiments, the fusion protein comprises an antibody that binds IL-6 or IL-6R and VEGFR ECD. In some embodiments, this fusion protein is selected from the following: anti-IL6-VEGFR, anti-IL6R-VEGFR (e.g., SEQ ID NOs: 324, 79).

In some embodiments, the fusion protein comprises an antibody that binds IL-6 or IL-6R, VEGFR ECD, and an additional receptor ECD. In one embodiment, VEGFR ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, VEGFR ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-IL6R-VEGFR-PD1 (e.g., SEQ ID NOs: 324, 314). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-IL6R-VEGFR-SIRPa (e.g., SEQ ID NOs: 324, 316). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL6R-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 324, 315).

In another embodiment, the ALT comprises an antibody that targets TGFb or TGFbR or GARP or LAP, wherein said antibody is fused to a ligand-binding sequence of an extracellular domain of VEGFR (VEGFR ECD). In another aspect an ALT comprises an antibody that targets TGFb or TGFbR, wherein said antibody is fused to a ligand-binding sequence of a VEGFR ECD, and additionally fused to a ligand-binding sequence of another different receptor ECD (receptor ECD-2). In various examples, receptor ECD-2 may be selected from a group comprising PD-1ECD, TIM-3ECD, BTLA ECD, or SIRPa. In one aspect, the VEGFR ECD sequence is fused to the C-terminus of the heavy chain of the targeting antibody, and another different receptor ECD-2 sequence is fused to the C-terminus of the light chain. In one aspect, the receptor ECD-2 fused to a TGFb or TGFbR targeting antibody binds to a cognate ligand expressed in the TME, thereby localizing the ALT and consequent VEGF/VEGFR and TGFb blockade to the TME. In one example, the receptor ECD-2 is a PD-1ECD sequence that binds PD-L1 or PD-L2 expressed on tumor cells or the TME. In another example, the receptor ECD-2 is a TIM-3ECD sequence that binds CEACAM-1 or CEACAM-5 or CEACAM-6 expressed on tumor cells or the TME. In another example, receptor ECD-2 is a BTLA ECD that binds HVEM expressed on tumor cells or the TME. In another example, the receptor ECD-2 is a SIRPa ECD sequence that binds CD47 expressed on tumor cells or the TME.

In some embodiments, the fusion protein comprises VEGFR ECD and a polypeptide that binds TGFb, TGFbR, or GARP. Exemplary embodiments of this fusion protein include anti-TGFb-VEGFR (e.g., SEQ ID NOs: 403, 133), anti-TGFbR-VEGFR, and anti-GARP-VEGFR (e.g., SEQ ID NOs: 415, 49).

In some embodiments, the fusion protein further comprises an additional receptor ECD. Exemplary embodiments of this fusion protein include anti-TGFb-VEGFR-SIRPa (e.g., SEQ ID NOs: 403, 396); anti-TGFb-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 403, 395); anti-TGFb-VEGFR-BTLA (e.g., SEQ ID NOs: 403, 399); anti-TGFb-VEGFR-TIM3 (e.g., SEQ ID NOs: 403, 397); anti-TGFb-VEGFR-PD1 (e.g., SEQ ID NOs: 403, 394).

In some embodiments, the fusion protein comprises VEGFR ECD and TGFbRII ECD. Exemplary embodiments of this fusion protein include VEGFR-Fc-TGFbRII (e.g., SEQ ID NO: 569) and TGFbRII-Fc-VEGFR (e.g., SEQ ID NO: 558).

In some embodiments, the fusion protein comprises VEGFR ECD and IL-15. In some embodiments, the fusion protein is IL15-Fc-VEGFR (e.g., SEQ ID NO: 598) or VEGFR-Fc-IL15 (e.g., SEQ ID NO: 597). In other embodiments, the fusion protein is IL12-Fc-VEGFR (e.g., SEQ ID NO: 596) or VEGFR-Fc-IL12 (e.g., SEQ ID NO: 595). In other embodiments, the fusion protein comprises an antibody with VEGFR ECD fused to heavy chain and IL-15 fused to light chain. In other embodiments, the fusion protein comprises an antibody with VEGFR ECD fused to heavy chain and IL-12 fused to light chain.

In various embodiments, the fusion proteins of the invention counteract TGFb in the tumor microenvironment. These fusion proteins are referred to as belonging to “Group 2”. In some embodiments, the fusion proteins comprise a ligand-binding sequence of an extracellular domain of TGFbR (e.g., TGFbRII ECD). In one embodiment, this ligand trap binds TGFb1, TGFb2, and/or TGFb3. In some embodiments, the TGFbR ECD may be a ligand-binding sequence of TGFbRII ECD. In some embodiments, the TGFbR ECD may be a fusion of domains from TGFbRII and TGFbRIII. In some embodiments, the TGFbR ECD may be selected from the following list: SEQ ID NOS: 177; 178; 179; 180.

In other embodiments, the fusion proteins of the invention comprise a targeting polypeptide that binds TGFb, TGFbR, LAP, or GARP fused to one or more receptor ECDs. These receptor ECDs are preferably selected from the following: PD1 ECD, TIM-3 ECD, VEGFR ECD, BTLA ECD, SIRPa ECD, SIGLEC 10 ECD. In some embodiments, the targeting polypeptide that binds TGFb, TGFbR, LAP, or GARP is an antibody.

In some embodiments, the ALT is a polypeptide comprising an antibody that targets TGFb or TGFbR, wherein said antibody is fused to a ligand-binding sequence of an extracellular domain of a Receptor. In one example, the ALT comprises an antibody that targets TGFb, wherein said antibody is fused to a ligand-binding sequence of an extracellular domain of Receptor (e.g. PD-1ECD, TIM-3ECD, VEGFR ECD, BTLA ECD, SIRPa ECD). In another aspect an ALT comprises an antibody that targets TGFb, wherein said antibody is fused to a ligand-binding sequence of a specific receptor ECD (receptor ECD-1), and additionally fused to a ligand-binding sequence of another different receptor ECD (receptor ECD-2). In various examples, receptor ECD-1 and receptor ECD-2 may be selected from a group comprising PD-1ECD, TIM-3ECD, VEGFR ECD, BTLA ECD, SIRPa ECD, SIGLEC10 ECD. In one aspect, the receptor ECD-1 sequence is fused to the C-terminus of the heavy chain of the targeting antibody, and another different receptor ECD-2 sequence is fused to the C-terminus of the light chain. In one aspect, the receptor ECD fused to a TGFb targeting antibody binds to a cognate ligand expressed in the TME, thereby localizing the ALT and consequent TGFb blockade to the TME. In one example, a PD-1ECD binds PD-L1 or PD-L2 expressed on tumor cells or the TME. In another example, a TIM-3ECD binds CEACAM-1 or CEACAM-5 or CEACAM-6 expressed on tumor cells or the TME. In another example, a BTLA ECD binds HVEM expressed on tumor cells or the TME. In another example, a SIRPa ECD binds CD47 expressed on tumor cells or the TME. Exemplary embodiments include anti-TGFb-PD1 (e.g., SEQ ID NOs: 398, 133); anti-TGFb-SIRPa (e.g., SEQ ID NOs: 401, 133); anti-TGFb-TIM3 (e.g., SEQ ID NOs: 402, 133); anti-TGFb-SIGLEC10 (e.g., SEQ ID NOs: 400, 133); anti-TGFb-BTLA (e.g., SEQ ID NOs: 393, 133); anti-TGFb-VEGFR (e.g., SEQ ID NOs: 403, 133)

Although CD47 targeted antibodies can promote antitumor immune responses by inhibiting the interaction of CD47 with SIRPa, its antitumor efficacy may be limited by TSP-1 dependent or TSP-1 independent activation of TGFb. In one embodiment, the ALT is a polypeptide comprising an antibody that targets CD47, wherein said antibody is fused to a TGFb-binding sequence from a extracellular domain of TGFbR (e.g. TGFbRII ECD). In this aspect, the ALT promotes antitumor immunity by disrupting the interaction of CD47 with SIRPa, while simultaneously counteracting TGFb-mediated immune dysfunction and angiogenesis. In another aspect, the ALT comprises a TGFb-binding sequence from one or more extracellular domains of TGFbR (e.g. TGFbRII ECD) and a CD47-binding sequence from one or more extracellular domains of SIRPa (SIRPa ECD).

Examples of fusion proteins of the invention that capture and disable TGFb in the TME include, but are not limited to the following: ALTs comprising an antibody fused to TGFbRECD (with or without another receptor ECD fused to the same antibody); ALTs where the antibody binds TGFb, TGFbR, LAP, or GARP, fused to one or more Receptor ECD(s).

In one aspect, the ALT is a polypeptide comprising an antibody fused to a TGFb-binding sequence from an extracellular domain of TGFbR (e.g. TGFbRII ECD). The TGFbRECD fused to the ALT localizes to the TME, where it serves as a decoy receptor to bind and disable TGFb (e.g TGFb1, TGFb2, TGFb3). In another aspect an ALT comprising a fused ligand-binding sequence of TGFbRECD is additionally fused to a different receptor ECD that captures and disables its cognate ligands (e.g. PD-1ECD, TIM-3ECD, VEGFR ECD, BTLA ECD, SIRPa ECD, SIGLEC10 ECD). In one aspect, the TGFbRECD is fused to the C-terminus of the heavy chain of the targeting antibody, and another different receptor ECD is fused to the C-terminus of the light chain. In one example, the TGFbRECD is fused to the C-terminus of the heavy chain of the targeting antibody, and a PD-1 ligand-binding sequence of PD-1ECD is fused to the C-terminus of the light chain. In another example, the TGFbRECD is fused to the C-terminus of the heavy chain of the targeting antibody, and a TIM-3 ligand-binding sequence of TIM-3ECD is fused to the C-terminus of the light chain. In another example, the TGFbRECD is fused to the C-terminus of the heavy chain of the targeting antibody, and a BTLA ligand-binding sequence of BTLA ECD is fused to the C-terminus of the light chain. In another example, the TGFbRECD is fused to the C-terminus of the heavy chain of the targeting antibody, and a CD47 ligand-binding sequence of SIRPa ECD is fused to the C-terminus of the light chain.

In some embodiments, the fusion protein comprises TGFbRII ECD and a polypeptide that inhibits the interaction between CD47 and SIRPa. In one embodiment, this fusion protein comprises TGFbRII ECD and a polypeptide that binds CD47. In one embodiment, this fusion protein is anti-CD47 mAb fused to TGFbRII ECD (anti-CD47-TGFbRII (e.g., SEQ ID NOs: 390, 22)). In another embodiment, this fusion protein comprises SIRPa ECD and TGFbRII ECD. In one embodiment, this fusion protein is SIRPa-Fc-TGFbRII (e.g., SEQ ID NO: 550) or TGFbRII-Fc-SIRPa (e.g., SEQ ID NO: 556).

In some embodiments, the fusion protein comprises TGFbRII ECD, a polypeptide that inhibits the interaction between CD47 and SIRPa, and another polypeptide. In a further embodiment, the fusion protein comprises TGFbRII ECD, a polypeptide that inhibits the interaction between CD47 and SIRPa, and another polypeptide that inhibits a T cell co-inhibitory molecule. In some embodiments, this fusion protein comprises anti-CD47 mAb with TGFbRII ECD fused to the heavy chain and a T cell co-inhibitory molecule ECD fused to the light chain. In a particular embodiment, this fusion protein is anti-CD47-TGFbRII-PD1 (e.g., SEQ ID NOs: 390, 384). In another embodiment, this fusion protein is anti-CD47-TGFbRII-BTLA (e.g., SEQ ID NOs: 390, 388). In another embodiment, this fusion protein is anti-CD47-TGFbRII-TIM3 (e.g., SEQ ID NOs: 390, 386).

In other embodiments, the fusion protein comprises TGFbRII ECD, SIRPa ECD, and an antibody with a heavy chain and light chain. In one embodiment, the TGFbRII ECD is fused to the heavy chain of the antibody and the SIRPa ECD is fused to the light chain of the antibody. In some embodiments, the antibody of said fusion protein binds a T cell co-inhibitory molecule as an antagonist. Exemplary embodiments of such fusion proteins include anti-CTLA4-TGFbRII-SIRPa (e.g., SEQ ID NOs: 444, 438), anti-PD1-TGFbRII-SIRPa (e.g., SEQ ID NOs: 456, 450), and anti-PDL1-TGFbRII-SIRPa (e.g., SEQ ID NOs: 466, 461). In other embodiments, the antibody of said fusion protein binds a T cell co-stimulatory molecule as an agonist. Exemplary embodiments of this fusion protein include anti-OX40-TGFbRII-SIRPa (e.g., SEQ ID NOs: 514, 508), anti-41BB-TGFbRII-SIRPa (e.g., SEQ ID NOs: 502, 496), and anti-CD40-TGFbRII-SIRPa. In other embodiments, the antibody of said fusion protein is a tumor-targeted antibody. In some embodiments, this tumor targeted-antibody binds a tumor growth factor or growth factor receptor. In other embodiments, this tumor targeted antibody binds a tumor cell surface molecule. Exemplary embodiments of this fusion protein include anti-EGFR-TGFbRII-SIRPa (e.g., SEQ ID NOs: 229, 223), anti-HER2-TGFbRII-SIRPa (e.g., SEQ ID NOs: 253, 247), anti-EGFRvIII-TGFbRII-SIRPa (e.g., SEQ ID NOs: 241, 235), anti-uPAR-TGFbRII-SIRPa, and anti-PSMA-TGFbRII-SIRPa.

In some embodiments, the fusion protein comprises TGFbRII ECD and a polypeptide that inhibits the interaction of BTLA and HVEM. In some embodiments, this fusion protein comprises an antibody that binds BTLA or HVEM fused to TGFbRII ECD. Exemplary embodiments of this fusion protein include anti-BTLA-TGFbRII and anti-HVEM-TGFbRII, BTLA-Fc-TGFbRII (e.g., SEQ ID NO: 532), and TGFbRII-Fc-BTLA (e.g., SEQ ID NO: 553).

In some embodiments, the fusion protein comprises TGFbRII ECD and a polypeptide that inhibits the interaction of TIGIT or PVRIG with PVRL2 or PVR. In some embodiments, this fusion protein comprises an antibody that binds TIGIT or PVRIG fused to TGFbRII ECD. Exemplary embodiments of this fusion protein include anti-TIGIT-TGFbRII (e.g., SEQ ID NOs: 478, 139) and anti-PVRIG-TGFbRII.

In some embodiments, the fusion protein comprises TGFbRII ECD and a polypeptide that inhibits the interaction of VISTA and VSIG8. In some embodiments, this fusion protein comprises an antibody that binds VISTA or VSIG8 fused to TGFbRII ECD. Exemplary embodiments of this fusion protein include anti-VISTA-TGFbRII and anti-VSIG8-TGFbRII.

In some embodiments, the fusion protein comprises TGFbRII ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and an additional receptor ECD. In one aspect, the TGFbRII ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody.

In some embodiments, the fusion protein comprises TGFbRII ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and PD1 ECD. Exemplary embodiments of this fusion protein include anti-TIGIT-TGFbRII-PD1 (e.g., SEQ ID NOs: 478, 470); anti-TIM3-TGFbRII-PD1 (e.g., SEQ ID NOs: 490, 482); anti-PD1-TGFbRII-PD1 (e.g., SEQ ID NOs: 456, 448); anti-CTLA4-TGFbRII-PD1 (e.g., SEQ ID NOs: 444, 436).

In other embodiments, the fusion protein comprises TGFbRII ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and BTLA ECD. Exemplary embodiments of this fusion protein include anti-TIGIT-TGFbRII-BTLA (e.g., SEQ ID NOs: 478, 475); anti-PDL1-TGFbRII-BTLA (e.g., SEQ ID NOs: 466, 464); anti-CTLA4-TGFbRII-BTLA (e.g., SEQ ID NOs: 444, 441); anti-PD1-TGFbRII-BTLA (e.g., SEQ ID NOs: 456, 453); anti-TIM3-TGFbRII-BTLA (e.g., SEQ ID NOs: 490, 487).

In other embodiments, the fusion protein comprises TGFbRII ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and TIM3 ECD. Exemplary embodiments of this fusion protein include anti-TIGIT-TGFbRII-TIM3 (e.g., SEQ ID NOs: 478, 473); anti-TIM3-TGFbRII-TIM3 (e.g., SEQ ID NOs: 490, 485); anti-CTLA4-TGFbRII-TIM3 (e.g., SEQ ID NOs: 444, 439); anti-PD1-TGFbRII-TIM3 (e.g., SEQ ID NOs: 456, 451); anti-PDL1-TGFbRII-TIM3 (e.g., SEQ ID NOs: 466, 462).

In other embodiments, the fusion protein comprises TGFbRII ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and SIRPa ECD. Exemplary embodiments of this fusion protein include anti-PDL1-TGFbRII-SIRPa (e.g., SEQ ID NOs: 466, 461); anti-CTLA4-TGFbRII-SIRPa (e.g., SEQ ID NOs: 444, 438); anti-TIM3-TGFbRII-SIRPa (e.g., SEQ ID NOs: 490, 484); anti-PD1-TGFbRII-SIRPa (e.g., SEQ ID NOs: 456, 450); anti-TIGIT-TGFbRII-SIRPa (e.g., SEQ ID NOs: 478, 472).

In other embodiments, the fusion protein comprises TGFbRII ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and SIGLEC10 ECD. Exemplary embodiments of this fusion protein include anti-CTLA4-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 444, 437); anti-PDL1-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 466, 460); anti-TIM3-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 490, 483); anti-PD1-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 456, 449); anti-TIGIT-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 478, 471).

In one embodiment, the fusion protein comprises a polypeptide that binds a T cell co-stimulatory molecule and TGFbRII ECD.

In some embodiments, the fusion protein is a native T cell co-stimulatory molecule ECD fused to TGFbRII (either N-costimulatory ECD-Fc-TGFbRII ECD-C, or N-TGFbRII ECD-Fc-costimulatory ECD-C). In some embodiments, this fusion protein is selected from: 41BBL-Fc-TGFbRII (e.g., SEQ ID NO: 616); ICOSL-Fc-TGFbRII (e.g., SEQ ID NO: 626); OX40L-Fc-TGFbRII (e.g., SEQ ID NO: 630), TGFbRII-Fc-ICOSL (e.g., SEQ ID NO: 625); TGFbRII-Fc-OX40L (e.g., SEQ ID NO: 629); TGFbRII-Fc-41BBL (e.g., SEQ ID NO: 615).

In other embodiments, the fusion protein comprises an antibody or other polypeptide that binds a T cell co-stimulatory molecule fused to TGFbRII. This antibody or polypeptide is preferably an agonist of the T cell co-stimulatory molecule. In some embodiments, this fusion protein is selected from: anti-ICOS-TGFbRII (e.g., SEQ ID NOs: 526, 59); anti-OX40-TGFbRII (e.g., SEQ ID NOs: 514, 97); anti-41BB-TGFbRII (e.g., SEQ ID NOs: 502, 2).

In a further aspect, the fusion protein comprises an antibody that binds a T cell-costimulatory molecule, TGFbRII ECD, and an additional receptor ECD. In one aspect, the TGFbRII ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-41BB-TGFbRII-PD1 (e.g., SEQ ID NOs: 502, 494); anti-OX40-TGFbRII-PD1 (e.g., SEQ ID NOs: 514, 506); anti-ICOS-TGFbRII-PD1 (e.g., SEQ ID NOs: 526, 518). In another embodiment, the T cell co-inhibitory molecule is BTLA. In some embodiments, the fusion protein is selected from: anti-OX40-TGFbRII-BTLA (e.g., SEQ ID NOs: 514, 511); anti-41BB-TGFbRII-BTLA (e.g., SEQ ID NOs: 502, 499); anti-ICOS-TGFbRII-BTLA (e.g., SEQ ID NOs: 526, 523). In another embodiment, the T cell co-inhibitory molecule is TIM3. In some embodiments, the fusion protein is selected from: anti-41BB-TGFbRII-TIM3 (e.g., SEQ ID NOs: 502, 497); anti-OX40-TGFbRII-TIM3 (e.g., SEQ ID NOs: 514, 509); anti-ICOS-TGFbRII-TIM3 (e.g., SEQ ID NOs: 526, 521). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-ICOS-TGFbRII-SIRPa (e.g., SEQ ID NOs: 526, 520); anti-41BB-TGFbRII-SIRPa (e.g., SEQ ID NOs: 502, 496); anti-OX40-TGFbRII-SIRPa (e.g., SEQ ID NOs: 514, 508). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-41BB-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 502, 495); anti-ICOS-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 526, 519); anti-OX40-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 514, 507).

In one embodiment, the fusion protein comprises TGFbRII ECD and a polypeptide that binds an ectonucleotidase. In a preferred embodiment, the ectonucleotidase is either CD39 or CD73. In some embodiments, the fusion protein comprises TGFbRII ECD, an antibody that binds CD39 or CD73, and an additional receptor ECD. In a preferred embodiment, the TGFbRII ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. In some embodiments, the fusion protein is selected from the following: anti-CD73-TGFbRII-SIRPa (e.g., SEQ ID NOs: 425, 419); anti-CD73-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 425, 418); anti-CD73-TGFbRII-BTLA (e.g., SEQ ID NOs: 425, 422); anti-CD73-TGFbRII-PD1 (e.g., SEQ ID NOs: 425, 417); anti-CD73-TGFbRII-TIM3 (e.g., SEQ ID NOs: 425, 420).

In some embodiments, the fusion protein comprises a tumor-targeted antibody and TGFbRII ECD. In some embodiments, this tumor targeted-antibody binds a tumor growth factor or growth factor receptor. In other embodiments, this tumor targeted antibody binds a tumor cell surface molecule. In some embodiments, this fusion protein is selected from the following: anti-EGFRvIII-TGFbRII (e.g., SEQ ID NOs: 241, 47), anti-uPAR-TGFbRII (e.g., SEQ ID NOs: 272, 162), anti-PSMA-TGFbRII (e.g., SEQ ID NOs: 279, 121), anti-nectin-4-TGFbRII.

In a further embodiment, the fusion protein comprises a tumor-targeted antibody, TGFbRII ECD, and an additional receptor ECD. In a preferred embodiment, the TGFbRII is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-HER2-TGFbRII-PD1 (e.g., SEQ ID NOs: 253, 245); anti-EGFR-TGFbRII-PD1 (e.g., SEQ ID NOs: 229, 221); anti-nectin4-TGFbRII-PD1 (e.g., SEQ ID NOs: 265, 257); anti-EGFRvIII-TGFbRII-PD1 (e.g., SEQ ID NOs: 241, 233). In another embodiment, the T cell co-inhibitory molecule is BTLA. In some embodiments, the fusion protein is selected from: anti-HER2-TGFbRII-BTLA (e.g., SEQ ID NOs: 253, 250); anti-EGFR-TGFbRII-BTLA (e.g., SEQ ID NOs: 229, 226); anti-EGFRvIII-TGFbRII-BTLA (e.g., SEQ ID NOs: 241, 238); anti-nectin4-TGFbRII-BTLA (e.g., SEQ ID NOs: 265, 262). In another embodiment, the T cell co-inhibitory molecule is TIM3. In some embodiments, the fusion protein is selected from: anti-EGFR-TGFbRII-TIM3 (e.g., SEQ ID NOs: 229, 224); anti-EGFRvIII-TGFbRII-TIM3 (e.g., SEQ ID NOs: 241, 236); anti-HER2-TGFbRII-TIM3 (e.g., SEQ ID NOs: 253, 248); anti-nectin4-TGFbRII-TIM3 (e.g., SEQ ID NOs: 265, 260). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-EGFR-TGFbRII-SIRPa (e.g., SEQ ID NOs: 229, 223); anti-nectin4-TGFbRII-SIRPa (e.g., SEQ ID NOs: 265, 259); anti-HER2-TGFbRII-SIRPa (e.g., SEQ ID NOs: 253, 247); anti-EGFRvIII-TGFbRII-SIRPa (e.g., SEQ ID NOs: 241, 235). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-nectin4-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 265, 258); anti-HER2-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 253, 246); anti-EGFRvIII-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 241, 234); anti-EGFR-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 229, 222).

In one aspect an ALT of the invention simultaneously counteracts VEGF and TGFb in the tumor microenvironment. In one example, the ALT comprises an antibody that targets either VEGF or VEGFR, wherein said antibody is fused to a TGFb-binding sequence of an extracellular domain of the TGFbR (e.g. TGFbRII ECD). In another aspect an ALT comprises an antibody that targets either VEGF or VEGFR, wherein said antibody is fused to a ligand-binding sequence of TGFbRECD, and additionally fused to a ligand-binding sequence of another different receptor ECD (receptor ECD-2). In various examples, receptor ECD-2 may be selected from a group comprising PD-1ECD, TIM-3ECD, BTLA ECD, or SIRPa ECD. In one aspect, the TGFb-binding TGFbRII ECD sequence is fused to the C-terminus of the heavy chain of the targeting antibody, and the receptor ECD-2 sequence is fused to the C-terminus of the light chain. In one aspect, the receptor ECD-2 sequence is fused to a VEGF or VEGFR targeting antibody; and binds to a cognate ligand expressed in the TME, thereby localizing the ALT and consequent VEGF/VEGFR and TGFb blockade to the TME. In one example, the receptor ECD-2 is a PD-1ECD sequence that binds PD-L1 or PD-L2 expressed on tumor cells or the TME. In another example, the receptor ECD-2 is a TIM-3ECD sequence that binds CEACAM-1 or CEACAM-5 or CEACAM-6 expressed on tumor cells or the TME. In another example, receptor ECD-2 is a BTLA ECD that binds HVEM expressed on tumor cells or the TME. In another example, the receptor ECD-2 is a SIRPa ECD sequence that binds CD47 expressed on tumor cells or the TME.

In some embodiments, the fusion protein comprises TGFbRII ECD and a polypeptide that inhibits VEGF/VEGFR signaling.

In some embodiments, the fusion protein comprises TGFbRII ECD and anti-VEGFR mAb. In some embodiments, this fusion protein is anti-VEGFR-TGFbRII (e.g., SEQ ID NOs: 381, 148). In a further embodiment, the fusion protein may additionally comprise a receptor ECD fused to the light chain of the antibody. In some embodiments, the fusion protein is selected from anti-VEGFR-TGFbRII-TIM3 (e.g., SEQ ID NOs: 381, 376); anti-VEGFR-TGFbRII-BTLA (e.g., SEQ ID NOs: 381, 378); anti-VEGFR-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 381, 374); anti-VEGFR-TGFbRII-PD1 (e.g., SEQ ID NOs: 381, 373); anti-VEGFR-TGFbRII-SIRPa (e.g., SEQ ID NOs: 381, 375).

In some embodiments, the fusion protein comprises TGFbRII ECD and anti-VEGF mAb. In some embodiments, this fusion protein is anti-VEGF-TGFbRII (e.g., SEQ ID NOs: 370, 32). In a further embodiment, the fusion protein may additionally comprise a receptor ECD fused to the light chain of the antibody. In some embodiments, the fusion protein is selected from anti-VEGF-TGFbRII-TIM3 (e.g., SEQ ID NOs: 370, 365); anti-VEGF-TGFbRII-SIRPa (e.g., SEQ ID NOs: 370, 364); anti-VEGF-TGFbRII-PD1 (e.g., SEQ ID NOs: 370, 362); anti-VEGF-TGFbRII-BTLA (e.g., SEQ ID NOs: 370, 367); anti-VEGF-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 370, 363).

In other embodiments, the fusion protein comprises TGFbRII ECD and VEGFR ECD. In one embodiment, this fusion protein is TGFbRII-Fc-VEGFR (e.g., SEQ ID NO: 558). In another embodiment, this fusion protein is VEGFR-Fc-TGFbRII (e.g., SEQ ID NO: 569).

In some embodiments, the fusion protein comprises an antibody that binds IL-17 or IL-17R and TGFbRII ECD. In some embodiments, this fusion protein is selected from the following: anti-IL17-TGFbRII, anti-IL17R-TGFbRII (e.g., SEQ ID NOs: 334, 63).

In a further embodiment, the fusion protein comprises an antibody that binds IL-17 or IL-17R, TGFbRII ECD, and an additional receptor ECD. In a preferred embodiment, the TGFbRII is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-IL17R-TGFbRII-PD1 (e.g., SEQ ID NOs: 334, 326). In another embodiment, the T cell co-inhibitory molecule is BTLA. In some embodiments, the fusion protein is selected from: anti-IL17R-TGFbRII-BTLA (e.g., SEQ ID NOs: 334, 331). In another embodiment, the T cell co-inhibitory molecule is TIM3. In some embodiments, the fusion protein is selected from: anti-IL17R-TGFbRII-TIM3 (e.g., SEQ ID NOs: 334, 329). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-IL17R-TGFbRII-SIRPa (e.g., SEQ ID NOs: 334, 328). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL17R-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 334, 327).

In some embodiments, the fusion protein comprises an antibody that binds IL-23 or IL-23R and TGFbRII ECD. If the antibody binds IL-23, it is preferred that the antibody bind the p19 subunit of IL-23 that is not shared with IL-12. In some embodiments, this fusion protein is selected from the following: anti-IL23-TGFbRII (e.g., SEQ ID NOs: 346, 75), anti-IL23R-TGFbRII.

In a further embodiment, the fusion protein comprises an antibody that binds IL-23 or IL-23R, TGFbRII ECD, and an additional receptor ECD. In a preferred embodiment, the TGFbRII is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-IL23-TGFbRII-PD1 (e.g., SEQ ID NOs: 346, 338). In another embodiment, the T cell co-inhibitory molecule is BTLA. In some embodiments, the fusion protein is selected from: anti-IL23-TGFbRII-BTLA (e.g., SEQ ID NOs: 346, 343). In another embodiment, the T cell co-inhibitory molecule is TIM3. In some embodiments, the fusion protein is selected from: anti-IL23-TGFbRII-TIM3 (e.g., SEQ ID NOs: 346, 341). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-IL23-TGFbRII-SIRPa (e.g., SEQ ID NOs: 346, 340). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL23-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 346, 339).

In some embodiments, the fusion protein comprises an antibody that binds IL-6 or IL-6R, TGFbRII ECD, and an additional receptor ECD. In a preferred embodiment, the TGFbRII is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-IL6R-TGFbRII-PD1 (e.g., SEQ ID NOs: 322, 314). In another embodiment, the T cell co-inhibitory molecule is BTLA. In some embodiments, the fusion protein is selected from: anti-IL6R-TGFbRII-BTLA (e.g., SEQ ID NOs: 322, 319). In another embodiment, the T cell co-inhibitory molecule is TIM3. In some embodiments, the fusion protein is selected from: anti-IL6R-TGFbRII-TIM3 (e.g., SEQ ID NOs: 322, 317). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-IL6R-TGFbRII-SIRPa (e.g., SEQ ID NOs: 322, 316). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL6R-TGFbRII-SIGLEC10 (e.g., SEQ ID NOs: 322, 315).

In some embodiments, the fusion protein comprises TGFbRII ECD and IL-15. In some embodiments, the fusion protein is IL15-Fc-TGFbRII (e.g., SEQ ID NO: 590) or TGFbRII-Fc-IL15 (e.g., SEQ ID NO: 589). In other embodiments, the fusion protein is IL12-Fc-TGFbRII (e.g., SEQ ID NO: 588) or TGFbRII-Fc-IL12 (e.g., SEQ ID NO: 587). In other embodiments, the fusion protein comprises an antibody with TGFbRII ECD fused to heavy chain and IL-15 fused to light chain. In other embodiments, the fusion protein comprises an antibody with TGFbRII ECD fused to heavy chain and IL-12 fused to light chain.

The data in Example 3 demonstrates that a fusion protein that blocks VEGF and also comprises the ECD of a molecule that inhibits immune cells (e.g., T cells, dendritic cells, macrophages) is effective in treating cancer. As such, in some embodiments of the invention, the fusion protein comprises a VEGF/VEGFR-blocking polypeptide and the ECD of an immuno-inhibitory receptor (e.g., SIRPa, SIGLEC10, PD1, BTLA, TIM-3). In other embodiments, the fusion protein comprises VEGFR ECD and an antibody that binds and disables the interaction of an immuno-inhibitory receptor and its ligand (e.g., anti-BTLA-VEGFR, anti-CD47-VEGFR, anti-PD1-VEGFR, anti-PDL1-VEGFR). In other embodiments, the fusion protein comprises VEGFR and the ECD of an immuno-inhibitory receptor (e.g., VEGFR-Fc-SIRPa, VEGFR-Fc-BTLA, VEGFR-Fc-SIGLEC10). In other embodiments, the fusion protein comprises anti-VEGF/VEGFR mAb and the ECD of an immuno-inhibitory receptor (e.g., anti-VEGF-SIRPa, anti-VEGF-BTLA, anti-VEGF-TIM3).

Furthermore, Example 3 demonstrates that a fusion protein that blocks VEGF and also comprises the ECD of a T cell co-inhibitory molecule is effective in treating cancer. As such, in some embodiments of the invention, the fusion protein comprises a VEGF/VEGFR-blocking polypeptide and the ECD of a T cell co-inhibitory molecule (e.g., PD1, BTLA, TIM-3).

Furthermore, Example 3 demonstrates that a fusion protein that blocks VEGF and also comprises a polypeptide that binds a tumor cell surface molecule or molecule enriched in the tumor microenvironment is effective in localizing VEGF to the tumor microenvironment. As such, in some embodiments of the invention, the fusion protein comprises a VEGF/VEGFR-blocking polypeptide and a polypeptide that binds a tumor cell surface molecule or molecule enriched in the tumor microenvironment. In some embodiments, this fusion protein comprises VEGFR ECD fused to an antibody that localizes to the TME (anti-nectin-4-VEGFR, anti-PSMA-VEGFR, anti-IL17R-VEGFR, anti-CD47-VEGFR). In other embodiments, this fusion protein comprises anti-VEGF/VEGFR antibody fused to a receptor ECD that localizes to the TME (e.g., anti-VEGF-BTLA, anti-VEGF-TIM3).

The data in Example 4 demonstrates that blockade of TGFb and VEGF is more effective in treatment of cancer than blockade of VEGF alone. As such, in some embodiments of the invention, the fusion protein comprises a polypeptide that inhibits TGFb and a polypeptide that inhibits VEGF. In some embodiments, this fusion protein comprises TGFbRII and VEGFR (e.g., TGFbRII-Fc-VEGFR). In other embodiments, the fusion protein comprises antibody that binds TGFb, TGFbR, LAP, or GARP and VEGFR (e.g., anti-TGFb-VEGFR). In other embodiments, the fusion protein comprises antibody that binds VEGF or VEGFR and TGFbRII ECD (e.g., anti-VEGF-TGFbRII, anti-VEGFR-TGFbRII).

Furthermore, Example 4 demonstrates that a fusion protein comprising an anti-VEGF/VEGFR polypeptide and another polypeptide that inhibits angiogenesis (e.g., TGFb) is effective in the treatment of cancer. As such, in some embodiments of the invention, the fusion protein comprises VEGFR ECD and a polypeptide that inhibits another determinant of angiogenesis. This additional determinant of angiogenesis may be TGFb, IL-17, or IL-17R. In some embodiments, this fusion protein is anti-TGFb-VEGFR, anti-IL17-VEGFR, anti-IL17R-VEGFR, or TGFbRII-Fc-VEGFR.

Furthermore, Example 4 demonstrates that a fusion protein comprising an antibody that inhibits angiogenesis fused to a receptor ECD that inhibits angiogenesis is effective in the treatment of cancer. As such, in some embodiments of the invention, the fusion protein comprises an antibody that inhibits angiogenesis (e.g., anti-VEGF, anti-VEGFR, anti-TGFb, anti-TGFbR, anti-IL-17, anti-IL17R) fused to a receptor ECD that inhibits angiogenesis (VEGFR ECD, TGFbRII ECD). Exemplary embodiments of these fusion proteins include anti-VEGF-TGFbRII, anti-IL17-TGFbRII, anti-IL17R-TGFbRII, anti-IL17-VEGFR, anti-IL17R-VEGFR, anti-TGFb-VEGFR.

Furthermore, Example 4 demonstrates that a fusion protein comprising anti-VEGF/VEGFR antibody and a receptor ECD that inhibits angiogenesis is effective in the treatment of cancer. As such, in some embodiments of the invention, the fusion protein comprises anti-VEGF/VEGFR mAb and a receptor ECD that inhibits angiogenesis. In some embodiments, this receptor ECD that inhibits angiogenesis is TGFbRII.

Furthermore, Example 4 demonstrates that a fusion protein comprising an anti-angiogenic polypeptide and a polypeptide that inhibits a key determinant of TH17 differentiation is effective in the treatment of cancer. As such, in some embodiments of the invention, the fusion protein comprises VEGFR and polypeptide that binds a key determinant of TH17 differentiation. In some embodiments, this key determinant of TH17 differentiation is TGFb/TGFbR, IL-6/IL-6R, IL-1/IL-1R, or IL-23/IL-23R. Exemplary embodiments of these fusion proteins include anti-IL23-TGFbRII, anti-IL23R-TGFbRII, anti-IL23-VEGFR, and anti-IL23R-VEGFR.

Furthermore, Example 4 demonstrates that localized blockade of VEGF and/or TGFb in the tumor microenvironment is effective in the treatment of cancer. As such, in some embodiments of the invention, a combination therapy of a tumor-localized inhibitor of VEGF is combined with an inhibitor of TGFb. In other embodiments, a combination therapy of a tumor-localized inhibitor of VEGF is combined with a tumor-localized inhibitor of TGFb. In other embodiments, a combination therapy of an inhibitor of VEGF is combined with a tumor-localized inhibitor of TGFb.

In some embodiments, tumor localization of VEGF inhibition is achieved via an ALT or ECD-ECD of the invention comprising VEGFR ECD and a polypeptide that binds a tumor cell surface molecule, cell surface molecule of a tumor-infiltrating immune cell, or other factor enriched in the tumor microenvironment. Exemplary embodiments of this agent include anti-CD47-VEGFR, anti-PDL1-VEGFR, anti-HER2-VEGFR, anti-EGFRvIII-VEGFR, anti-PSMA-VEGFR, anti-nectin-4-VEGFR. Further exemplary embodiments of this agent that localize to tumor-infiltrating T cells (e.g., tumor-infiltrating Tregs) include anti-CD39-VEGFR, anti-CD73-VEGFR, anti-CTLA4-VEGFR. In a further embodiment, the localizing polypeptide of the VEGFR-containing fusion protein is a receptor ECD. Exemplary embodiments of this fusion protein include VEGFR-Fc-SIRPa, VEGFR-Fc-BTLA, VEGFR-Fc-PD1, VEGFR-Fc-TIM3. In other embodiments, tumor localization of VEGF inhibition is achieved by an ALT of the invention comprising anti-VEGF/VEGFR mAb fused to a receptor ECD that binds a tumor cell or tumor-infiltrating immune cell. Exemplary embodiments of this agent include anti-VEGF-SIRPa, anti-VEGF-SIGLEC10, anti-VEGF-BTLA, anti-VEGF-TIM3, anti-VEGF-PD1.

In some embodiments, tumor localization of TGFb inhibition is achieved via an ALT or ECD-ECD of the invention comprising TGFbRII ECD and a polypeptide that binds a tumor cell surface molecule, cell surface molecule of a tumor-infiltrating immune cell, or other factor enriched in the tumor microenvironment. Exemplary embodiments of this agent include anti-CD47-TGFbRII, anti-PDL1-TGFbRII, anti-HER2-TGFbRII, and anti-nectin-4-TGFbRII. Further exemplary embodiments of this agent that localize to tumor-infiltrating T cells (e.g., tumor-infiltrating Tregs) include anti-CD39-TGFbRII, anti-CD73-TGFbRII, anti-CTLA4-TGFbRII. In a further embodiment, the localizing polypeptide of the TGFbRII-containing fusion protein is a receptor ECD. Exempary embodiments of this fusion protein include TGFbRII-Fc-SIRPa, TGFbRII-Fc-BTLA, TGFbRII-Fc-PD1, TGFbRII-Fc-TIM3. In other embodiments, tumor localization of TGFb inhibition is achieved by an ALT of the invention comprising anti-TGFb/TGFbR/GARP/LAP mAb fused to a receptor ECD that binds a tumor cell or tumor-infiltrating immune cell. Exemplary embodiments of this agent include anti-TGFb-SIRPa, anti-TGFb-SIGLEC10, anti-TGFb-BTLA, anti-TGFb-TIM3, anti-TGFb-PD1.

In some embodiments, the VEGF inhibitor is selected from the following: anti-VEGF antibody (e.g., bevacizumab), VEGFR antibody (e.g. ramucirumab), VEGFR kinase inhibitor (e.g., sunitinib, sorafenib, axitinib, cabozantinib, regorafenib, pazopanib, vandetanib, lenvatenib), or VEGFRecd-Fc fusion protein (e.g., aflibercept), or ALT comprising a ligand-binding sequence of VEGFRecd.

In some embodiments, the TGFb inhibitor is selected from the following: TGFbRI kinase inhibitor (e.g., galunisertib), anti-TGFb antibody (e.g., fresolimumab), anti-GARP antibody, anti-LAP antibody, anti-TGFbR antibody, fusion protein comprising TGFbRecd (e.g., TGFbRII-Fc), ALT comprising TGFbRecd (e.g., anti-PDL1-TGFbRIIecd, M7824, bintrafusp alfa, anti-CD73-TGFbRII, anti-CD39-TGFbRII).

The data in Example 5 demonstrate that tumor-targeted TGFbRII is effective in treating cancer. As such, in some embodiments of the invention, the fusion protein comprises TGFbRII ECD and a polypeptide that localizes the fusion protein to the tumor microenvironment. Exemplary embodiments of this fusion protein include anti-EGFRvIII-TGFbRII, anti-PSMA-TGFbRII, anti-nectin-4-TGFbRII, anti-CD47-TGFbRII.

Furthermore, Example 5 demonstrates that fusion proteins comprising TGFbRII and a polypeptide that induces or promotes ADCC/FcR-mediated cross-presentation is effective in treating cancer. As such, in some embodiments of the invention, the fusion protein comprises TGFbRII and an antibody that induces or promotes ADCC/FcR-mediated cross-presentation. In some embodiments, this fusion protein promotes ADCC/FcR-mediated cross-presentation by disabling a “don't eat me” signal on the tumor cell. In some embodiments, this “don't eat me” signal is CD47/SIRPa, SIGLEC10/CD24, CD31/CD31, or LILRB1/MHC. Exemplary embodiments of this fusion protein include anti-CD47-TGFbRII and SIRPa-Fc-TGFbRII and SIGLEC10-Fc-TGFbRII.

Furthermore, the invention comprises methods of treatment of cancer comprising one agent that is a TGFbRII-comprising fusion protein and another agent that promotes ADCC/FcR-mediated cross-presentation. In some embodiments, the TGFbRII-comprising fusion protein is an ALT or ECD-ECD comprising TGFbRII. In a particular aspect, the TGFbRII-comprising fusion protein comprises an antibody that binds a tumor cell surface molecule or tumor-infiltrating T cell cell surface molecule. Exemplary TGFbRII-comprising fusion proteins that bind tumor cell surface molecules include anti-EGFR-TGFbRII, anti-HER2-TGFbRII, anti-PSMA-TGFbRII, anti-nectin-4-TGFbRII, anti-IL17R-TGFbRII, and anti-PDL1-TGFbRII. Exemplary TGFbRII-comprising fusion proteins that bind tumor-infiltrating T cell cell surface molecules include anti-CD73-TGFbRII, anti-CD39-TGFbRII, anti-CTLA4-TGFbRII. Exemplary agents that promote ADCC/FcR-mediated cross presentation include anti-CD47, SIRPa-Fc, ALTs comprising anti-CD47, and ALTs comprising SIRPa ECD. Exemplary embodiments of this method of treatment include combination of anti-CD47 mAb with anti-CD73-TGFbRII, anti-CD47 mAb with anti-CD39-TGFbRII, anti-CD47 with anti-PDL1-TGFbRII, or anti-CD47 with anti-CTLA4-TGFbRII.

Furthermore, the invention comprises methods of treatment of cancer comprising one agent that blocks TGFb in the tumor microenvironment, and another agent that promotes ADCC/FcR-mediated cross-presentation. In some embodiments, the agent that blocks TGFb in the tumor microenvironment comprises an antibody to TGFb, TGFbR, LAP, or GARP fused to a receptor ECD that binds a tumor cell surface molecule or tumor-infiltrating T cell cell surface molecule (e.g., SIRPa ECD, BTLA ECD, TIM-3 ECD, PD-1 ECD, SIGLEC10 ECD).

In another aspect, fusion proteins of the invention counteract ITIM/ITSM signaling in the TME. In one embodiment, the fusion protein of the invention counteracts an immune cell inhibitory molecule that inhibits immune cell signaling, TCR signaling, T cell activation, macrophage phagocytosis, or dendritic cell antigen cross-presentation. In one embodiment, the immune cell inhibitor molecule exerts its inhibitor function via ITIMs or ITSMs. In one embodiment, the molecule of the invention comprises a ligand-binding sequence of the extracellular domain of a T cell co-inhibitory molecule (and is devoid of the transmembrane and intracellular domains containing ITIM or ITSM). In one aspect, the ligand-binding sequence of the extracellular domain of the T cell co-inhibitory molecule serves as a decoy or ligand-trap that binds its cognate ligand(s), thereby preventing ITIM/ITSM signaling by inhibiting the interaction of the ligand with the co-inhibitory molecule on the immune cell. In various examples, the molecule contains a ligand-binding sequence of the extracellular domain of PD-1 (PD1 ECD). In various examples, the molecule contains a ligand-binding sequence of the extracellular domain of TIM3 (TIM3 ECD). In various examples, the molecule contains a ligand-binding sequence of the extracellular domain of BTLA (BTLA ECD). In another aspect, the molecule of the invention comprises a ligand-binding sequence of the extracellular domain of an immune inhibitory molecule that exerts its inhibitory function via ITIMs and/or ITSMs. In various examples, the molecule contains a ligand-binding sequence of the extracellular domain of SIRPa (SIRPa ECD). In various examples, the molecule contains a ligand-binding sequence of the extracellular domain of SIGLEC10 (SIGLEC10 ECD).

In another embodiment, the molecule of the invention comprises a targeting polypeptide that binds either the immune cell inhibitory receptor or ligand to prevent the interaction leading to ITIM/ITSM-mediated inhibition, fused to one or more receptor ECDs. In one embodiment, the targeting polypeptide is an antibody. In various examples, the targeting polypeptide binds and disables CD24 or SIGLEC10; PD-1 or PD-L1; SIRPa or CD47; TIM-3 or a CEACAM family member that binds TIM-3; BTLA or HVEM. In various examples, the targeting polypeptide is an antibody that binds and disables CD24, SIGLEC10, PD-1, PD-L1, SIRPa, CD47, TIM-3, a CEACAM family member, BTLA, or HVEM.

As shown in Example 2, antibody-ligand traps containing BTLAecd localize to HVEM-expressing cells and simultaneously counteract BTLA-mediated suppression & promote HVEM-mediated activation of T cells. BTLA ligation by HVEM inhibits T cell activation via SHP-1-mediated inhibition of CD28 and CD3z signaling. HVEM ligation by LIGHT or BTLA (in trans) promotes T cell activation. The antibody ligand traps of the invention comprising a BTLA ecd which binds HVEM, thereby disrupting its interaction with both BTLA and CD160. In addition, ligation of T cell HVEM by BTLAecd of the ALT may promote HVEM-mediated costimulatory signals for T cell activation. PD-1 ligation by PD-1 ligands (PD-L1 or PD-L2) inhibits T cell activation via SHP-2-mediated inhibition of CD28 signaling. The interaction of PD-L1 with PD-1 can be disrupted by antibodies targeting either PD-L1 or PD-1, or a PD1 ecd that binds both PD-L1 and PD-L2. Antibody ligand traps comprising a BTLA ecd fused to an antibody that specifically binds PD-L1, or PD-1 can simultaneously inhibit PD-L1/PD-1 and HVEM/BTLA induced SHP1/2 mediated suppression of CD28 and CD3 signaling. As such, these molecules of the invention can counteract both HVEM/BTLA and PD-L1 mediated immune suppression in the tumor environment, thereby enhancing antitumor immune responses.

The data in Example 2 demonstrate that BTLA ECD fused to the heavy or light chain of an antibody is capable of binding HVEM, thereby disrupting native BTLA-mediated SHP1/SHP2 inhibition, and promoting HVEM-mediated co-stimulatory signaling. As such, in some embodiments, the fusion proteins of the invention comprise an antibody and BTLA ECD where BTLA ECD is fused to either light chain or heavy chain of antibody. In one aspect, the BTLAecd is fused to the heavy chain of an antibody, with or without a linker. In a further aspect, BTLAecd is fused to the C terminus of immunoglobulin Fc, with or without a linker. In one aspect, BTLAecd is fused to the light chain of an antibody, with or without a linker. In a further aspect, BTLAecd is fused to the C terminus of the light chain, with or without a linker.

Furthermore, Example 2 demonstrates that inhibition of BTLA/HVEM signaling with a decoy BTLA receptor ECD fused to a polypeptide that binds and disables another immuno-inhibitory molecule is effective in the treatment of cancer. As such, in some embodiments, the fusion proteins of the invention comprise a BTLA ECD and a targeting polypeptide that specifically binds an immune cell inhibitory molecule that inhibits the function of T cells, macrophages and/or dendritic cells. In one aspect, the immune cell inhibitory molecule has an intracellular domain comprising ITIM or ITSM motifs. In one aspect, the inhibitory molecule is a ligand that binds an inhibitory receptor containing ITIM or ITSM motifs. In one aspect, the inhibitory receptor signals via SHP1 or SHP2. In one aspect, the targeting polypeptide inhibits the function of the immune cell inhibitory molecule as an antagonist. In one aspect, the targeting polypeptide is an antibody. In another aspect, the targeting polypeptide is a Fc fusion protein. Examples of the immuno-inhibitory molecules include, but are not limited to the following: CD47, SIRPa, CD24, SIGLEC-10, LILRB, PD-L1, PD-L2, PD1, TIGIT, PVRIG, TIM-3, CEACAM1, CEACAM5.

Furthermore, Example 2 demonstrates that the decoy BTLA receptor ECD fused to a polypeptide that binds and disables another T cell co-inhibitory molecule is effective in the treatment of cancer. As such, in some fusion proteins, BTLA ECD is fused to a targeting polypeptide that specifically binds a T cell co-inhibitory molecule. In one aspect, the targeting polypeptide inhibits the function of the T cell co-inhibitory molecule. In one aspect, the targeting polypeptide is an antibody. In another aspect, the targeting polypeptide is a Fc fusion protein. Examples of the T cell co-inhibitory molecule include, but are not limited to the following: PD-L1, PD-L2, PD1, CTLA-4, TIGIT, PVRIG, TIM-3, TIM-3 ligand, CEACAM1, CEACAM5, VISTA, VSIG8.

Furthermore, Example 2 demonstrates that decoy BTLA receptor ECD fused to a polypeptide that inhibits the interaction of a cytokine and its cytokine receptor is effective in the treatment of cancer. As such, in some embodiments of the invention, BTLA ECD is fused to a targeting polypeptide that specifically binds a cytokine or cytokine receptor. In one aspect, the cytokine or cytokine receptor inhibit the function of T cells, macrophages, and/or dendritic cells. In one aspect, the cytokine or cytokine receptor promote tumor angiogenesis. In one aspect, the targeting polypeptide is an antibody. In another aspect, the targeting polypeptide is a ligand-binding sequence of a cytokine receptor extracellular domain. Examples of the cytokine/cytokine receptor include TGFb/TGFbR, IL-17/IL-17R, IL-23/IL-23R, IL-6/IL-6R, IL-1/IL-1R, IL-10/IL-10R, and VEGF/VEGFR.

Furthermore, Example 2 demonstrates that decoy BTLA receptor ECD fused to a polypeptide that binds a tumor cell surface molecule is effective in the treatment of cancer. As such, in some embodiments of the invention, BTLA ECD is fused to a polypeptide that binds a tumor cell surface molecule. In some embodiments, this tumor cell-surface molecule is a growth factor or growth factor receptor. In other embodiments, this tumor cell surface molecule is a protein that is overexpressed on tumor cells. Examples of the tumor cell surface molecule include PD-L1, EGFR, HER2, EGFRvIII, PSMA, nectin-4, and uPAR. In a particular aspect, the targeting polypeptide is a bispecific antibody. In a further aspect, the bispecific antibody is a CrossMab or a BiTE. In a further aspect, the bispecific antibody binds CD3 and a tumor cell surface molecule. Examples of the bispecific antibody include CD3×HER2 bsAbs and CD3×CEA bsAbs.

Furthermore, Example 2 demonstrates that decoy BTLA receptor ECD on either the heavy or light chain of the targeting polypeptide is capable of binding HVEM, thereby disrupting native BTLA-mediated SHP1/SHP2 inhibition and promoting HVEM-mediated co-stimulatory signaling, even while another receptor ECD is additionally fused to the antibody. Furthermore, these data demonstrate that decoy BTLA receptor ECD is effective in the treatment of cancer when part of a fusion protein comprising an additional ECD of a cytokine or cytokine receptor. As such, in some embodiments of the invention, the fusion protein comprising BTLA ECD further comprises an additional ECD (ECD #2) selected from: TGFbRII ECD, VEGFR ECD, SIRPa ECD, SIGLEC10 ECD, ECD of a T cell co-inhibitory molecule (e.g., TIM3 ECD, or PD1 ECD). In other embodiments, the fusion protein comprising BTLA ECD further comprises an additional ECD (ECD #2) of a cytokine. In some embodiments, this cytokine is IL-15 or IL-12. In some embodiments, BTLA ECD is fused to the heavy chain or light chain of the targeting antibody and ECD #2 is fused to the heavy or light chain. In some embodiments, ECD #2 is fused to the heavy chain. In other embodiments, ECD #2 is fused to the light chain. In some embodiments, ECD #2 is TGFbRII ECD. In other embodiments, ECD #2 is a ligand-binding fragment of a T cell co-inhibitory molecule. In some embodiments, ECD #2 is TIM3 ECD. In other embodiments, ECD #2 is VEGFR ECD. In other embodiments, ECD #2 is a cytokine receptor ECD. In other embodiments, ECD #2 is the ECD of a receptor whose ligation inhibits phagocytosis. In some embodiments, ECD #2 is SIRPa ECD or SIGLEC10 ECD. In other embodiments, BTLA ECD and ECD #2 are fused together, with or without a linker; with or without an Fc domain between them.

Furthermore, Example 2 demonstrates that decoy BTLA receptor ECD fused to an antibody can enable recruitment of T cells to tumor cells, since these data show that BTLA ECD can bind HVEM while the targeting antibody simultaneously binds a T cell surface molecule. As such, in some embodiments of the invention, BTLA ECD is fused to an antibody that binds T cells. In some embodiments, the antibody binds CD3. In a particular aspect, the antibody is a bispecific antibody. In a further aspect, the antibody is a bispecific antibody that binds CD3 and another target.

In various embodiments, the fusion proteins of the invention counteract PD-1/PD-L1 in the tumor microenvironment. In some embodiments, the fusion proteins comprise a ligand-binding sequence of an extracellular domain of PD-1 (e.g., PD1 ECD).

In one embodiment, the fusion protein of the invention comprises an antibody that binds PD1 or PD-1 ligand. In one example, the ALT comprises an antibody that binds PD1 and interferes with its interaction with PD-1 ligand. In one example, the ALT comprises an antibody that binds PDL1 and interferes with its interaction with PD-1 or B7. In one aspect, the antibody is an antagonist that inhibits PD1/PD1 ligand interaction or intracellular ITIM or ITSM signaling, thereby promoting immune cell activation. In various examples, the antibody that binds PD1 or PD1 ligand is fused to one or more ligand traps. In one example the PD1 or PDL1 antibody is fused to a ligand-binding sequence of the extracellular domain of TIM3 (TIM3 ECD). In one example the PD1 or PDL1 antibody is fused to a ligand-binding sequence of the extracellular domain of TGFbR (TGFbRII ECD). In one example the PD1 or PDL1 antibody is fused to a ligand-binding sequence of the extracellular domain of BTLA (BTLA ECD). In one example the PD1 or PDL1 antibody is fused to a ligand-binding sequence of the extracellular domain of SIRPa (SIRPa ECD). In one example the PD1 or PDL1 antibody is fused to a ligand-binding sequence of the extracellular domain of VEGFR (VEGFR ECD). In one embodiment, the PD1 or PDL1 binding antibody is fused to multiple ligand traps selected from the following: TIM3 ECD, TGFbRII ECD, BTLA ECD, SIRPa ECD, VEGFR ECD. In one aspect, a ligand trap is fused to the heavy chain, and a second ligand trap is fused to the light chain.

In various examples, the ALT comprises a PD1 or PDL1 binding antibody, wherein the heavy chain is fused to TGFbRII ECD and the light chain is fused to TIM3 ECD or BTLA ECD or SIRPa ECD or SIGLEC10 ECD. In various examples, the ALT comprises a PD1 or PDL1 binding antibody, wherein the heavy chain is fused to TIM3 ECD and the light chain is fused to BTLA ECD or SIRPa ECD or SIGLEC10 ECD. In various examples, the ALT comprises a PD1 or PDL1 binding antibody, wherein the heavy chain is fused to BTLA ECD and the light chain is fused to TIM3 ECD or SIGLEC10 ECD or SIRPa ECD.

In various examples, the ALT comprises a PD1 or PDL1 binding antibody, wherein the heavy chain is fused to VEGFR ECD and the light chain is fused to TIM3 ECD, SIGLEC10 ECD, SIRPa ECD, or BTLA ECD.

In one embodiment, the fusion proteins of the invention may comprise a ligand-binding sequence of an extracellular domain of Programmed-Death 1 (PD1). In one aspect, the PD1 ECD binds and disables PD-L1 or PD-L2. In one aspect, the PD1 ECD interferes with the interaction of PD1 ligands with either PD1 or B7.

In some embodiments, the fusion protein of the invention comprises a targeting polypeptide that is an antibody. In one embodiment, the antibody is fused to PD1 ECD and additional ligand traps selected from the following: TIM3 ECD, TGFbRII ECD, BTLA ECD, SIRPa ECD, VEGFR ECD, SIGLEC10 ECD. In one aspect, a ligand trap (LT1) is fused to the heavy chain, and a second ligand trap (LT2) is fused to the light chain. In one aspect, the PD1 ECD is fused to the heavy chain and another ligand trap is fused to the light chain. In one aspect, the PD1 ECD is fused to the light chain and another ligand trap is fused to the heavy chain. In various examples, the ALT comprises an antibody, wherein the heavy chain is fused to PD1 ECD and the light chain is fused to one of TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD. In various examples, the ALT comprises an antibody wherein the light chain is fused to PD1 ECD and the heavy chain is fused to one of TIM3 ECD, TGFbRII ECD, BTLA ECD, SIRPa ECD, VEGFR ECD, SIGLEC10 ECD.

In some embodiments, the fusion protein comprises PD1 ECD and a polypeptide that inhibits the interaction between CD47 and SIRPa. In one embodiment, this fusion protein comprises PD1 ECD and a polypeptide that binds CD47. In one embodiment, this fusion protein is anti-CD47 mAb fused to PD1 ECD (anti-CD47-PD1 (e.g., SEQ ID NOs: 387, 22)). In another embodiment, this fusion protein comprises SIRPa ECD and PD1 ECD. In one embodiment, this fusion protein is SIRPa-Fc-PD1 (e.g., SEQ ID NO: 548) or PD1-Fc-SIRPa (e.g., SEQ ID NO: 537).

In another aspect, the fusion protein comprises PD1 ECD, SIRPa ECD, and an antibody with a heavy chain and light chain. In one aspect, the PD1 ECD is fused to the heavy chain of the antibody and the SIRPa ECD is fused to the light chain of the antibody. In another aspect, the PD1 ECD is fused to the light chain of the antibody and the SIRPa ECD is fused to the heavy chain of the antibody. In some embodiments, the antibody of said fusion protein binds a T cell co-inhibitory molecule as an antagonist. An exemplary embodiment of such a fusion protein includes anti-CTLA4-PD1-SIRPa (e.g., SEQ ID NOs: 440, 438). In other embodiments, the antibody of said fusion protein binds a T cell co-stimulatory molecule as an agonist. Exemplary embodiments of this fusion protein include anti-OX40-PD1-SIRPa (e.g., SEQ ID NOs: 510, 508), anti-41BB-PD1-SIRPa (e.g., SEQ ID NOs: 498, 496), and anti-CD40-PD1-SIRPa. In other embodiments, the antibody of said fusion protein is a tumor-targeted antibody. In some embodiments, this tumor targeted-antibody binds a tumor growth factor or growth factor receptor. In other embodiments, this tumor targeted antibody binds a tumor cell surface molecule. Exemplary embodiments of this fusion protein include anti-EGFR-PD1-SIRPa (e.g., SEQ ID NOs: 225, 223), anti-HER2-PD1-SIRPa (e.g., SEQ ID NOs: 249, 247), anti-EGFRvIII-PD1-SIRPa (e.g., SEQ ID NOs: 237, 235), anti-uPAR-PD1-SIRPa, and anti-PSMA-PD1-SIRPa.

In other embodiments, the antibody of said fusion protein binds a member of the TGFb pathway. In some embodiments, this antibody binds TGFb, TGFbR, or GARP. Exemplary embodiments of this fusion protein include anti-TGFb-PD1-SIRPa (e.g., SEQ ID NOs: 398, 396), anti-TGFbR-PD1-SIRPa, and anti-GARP-PD1-SIRPa.

In other embodiments, the antibody of said fusion protein binds VEGF or VEGFR. Exemplary embodiments of this fusion protein include anti-VEGF-PD1-SIRPa (e.g., SEQ ID NOs: 366, 364) and anti-VEGFR-PD1-SIRPa (e.g., SEQ ID NOs: 377, 375).

In some embodiments, the fusion protein comprises PD1 ECD and a polypeptide that inhibits a T cell co-inhibitory molecule. In specific embodiments, the fusion protein comprises PD1 ECD and an antibody that binds and disables a T cell co-inhibitory molecule. In various examples, the T cell co-inhibitory molecule is CTLA-4, LAG3, TIM-3, CEACAM, CD47, SIRPa, TIGIT, VISTA, VSIG8, PVRIG, or BTLA.

In some embodiments, the fusion protein comprises PD1 ECD and a polypeptide that inhibits the interaction of TIGIT or PVRIG with PVRL2 or PVR. In some embodiments, this fusion protein comprises an antibody that binds TIGIT or PVRIG fused to PD1 ECD. Exemplary embodiments of this fusion protein include anti-TIGIT-PD1 (e.g., SEQ ID NOs: 474, 139) and anti-PVRIG-PD1.

In some embodiments, the fusion protein comprises PD1 ECD and a polypeptide that inhibits the interaction of VISTA and VSIG8. In some embodiments, this fusion protein comprises an antibody that binds VISTA or VSIG8 fused to PD1 ECD. Exemplary embodiments of this fusion protein include anti-VISTA-PD1 and anti-VSIG8-PD1.

In some embodiments, the fusion protein comprises PD1 ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and an additional receptor ECD. In one aspect, the PD1 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the PD1 ECD is fused to the light chain and the additional receptor ECD is fused to the heavy chain.

In other embodiments, the fusion protein comprises PD1 ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and SIRPa ECD. Exemplary embodiments of this fusion protein include anti-PD1-PD1-SIRPa (e.g., SEQ ID NOs: 452, 450); anti-CTLA4-PD1-SIRPa (e.g., SEQ ID NOs: 440, 438); anti-TIGIT-PD1-SIRPa (e.g., SEQ ID NOs: 474, 472); anti-TIM3-PD1-SIRPa (e.g., SEQ ID NOs: 486, 484).

In other embodiments, the fusion protein comprises PD1 ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and SIGLEC10 ECD. Exemplary embodiments of this fusion protein include anti-TIGIT-PD1-SIGLEC10 (e.g., SEQ ID NOs: 474, 471); anti-PD1-PD1-SIGLEC10 (e.g., SEQ ID NOs: 452, 449); anti-CTLA4-PD1-SIGLEC10 (e.g., SEQ ID NOs: 440, 437); anti-TIM3-PD1-SIGLEC10 (e.g., SEQ ID NOs: 486, 483).

In a further aspect, the fusion protein comprises an antibody that binds a T cell-costimulatory molecule, PD1 ECD, and an additional receptor ECD. In one aspect, the PD1 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the PD1 ECD is fused to the light chain of the antibody and the additional receptor ECD is fused to the heavy chain of the antibody. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-ICOS-PD1-SIRPa (e.g., SEQ ID NOs: 522, 520); anti-OX40-PD1-SIRPa (e.g., SEQ ID NOs: 510, 508); anti-41BB-PD1-SIRPa (e.g., SEQ ID NOs: 498, 496). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-OX40-PD1-SIGLEC10 (e.g., SEQ ID NOs: 510, 507); anti-ICOS-PD1-SIGLEC10 (e.g., SEQ ID NOs: 522, 519); anti-41BB-PD1-SIGLEC10 (e.g., SEQ ID NOs: 498, 495).

In some embodiments, the fusion protein comprises an antibody, PD1 ECD, and the ECD of a T cell co-stimulatory molecule. In one aspect, the PD1 ECD is fused to heavy chain and the ECD of a T cell co-stimulatory molecule fused to light chain. Alternatively, the PD1 ECD is fused to the light chain and the T cell co-stimulatory molecule ECD is fused to the heavy chain. In some embodiments, the fusion protein comprises PD1 ECD and one of the following: OX40L, 41BBL, ICOSL.

In one embodiment, the fusion protein comprises PD1 ECD and a polypeptide that binds an ectonucleotidase. In a preferred embodiment, the ectonucleotidase is either CD39 or CD73. In some embodiments, the fusion protein is an antibody that binds CD39 or CD73 fused to PD1 ECD; for example: anti-CD39-PD1 (e.g., SEQ ID NOs: 429, 18) or anti-CD73-PD1 (e.g., SEQ ID NOs: 421, 24).

In some embodiments, the fusion protein comprises PD1 ECD, an antibody that binds CD39 or CD73, and an additional receptor ECD. In some embodiments, the PD1 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the PD1 ECD is fused to the light chain of the antibody and the additional receptor ECD is fused to the heavy chain of the antibody. In some embodiments, the fusion protein is selected from the following: anti-CD39-PD1-SIRPa, or anti-CD73-PD1-SIRPa (e.g., SEQ ID NOs: 421, 419).

In some embodiments, the fusion protein comprises a tumor-targeted antibody and PD1 ECD. In some embodiments, this tumor targeted-antibody binds a tumor growth factor or growth factor receptor. In other embodiments, this tumor targeted antibody binds a tumor cell surface molecule. In some embodiments, this fusion protein is selected from the following: anti-EGFR-PD1 (e.g., SEQ ID NOs: 225, 43), anti-HER2-PD1 (e.g., SEQ ID NOs: 249, 55), anti-EGFRvIII-PD1 (e.g., SEQ ID NOs: 237, 47), anti-uPAR-PD1 (e.g., SEQ ID NOs: 269, 162), anti-PSMA-PD1 (e.g., SEQ ID NOs: 276, 121).

In a further embodiment, the fusion protein comprises a tumor-targeted antibody, PD1 ECD, and an additional receptor ECD. In one embodiment, the PD1 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the PD1 ECD is fused to the light chain and the additional receptor ECD is fused to the heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-EGFR-PD1-SIRPa (e.g., SEQ ID NOs: 225, 223); anti-HER2-PD1-SIRPa (e.g., SEQ ID NOs: 249, 247); anti-EGFRvIII-PD1-SIRPa (e.g., SEQ ID NOs: 237, 235); anti-nectin4-PD1-SIRPa (e.g., SEQ ID NOs: 261, 259). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-EGFR-PD1-SIGLEC10 (e.g., SEQ ID NOs: 225, 222); anti-nectin4-PD1-SIGLEC10 (e.g., SEQ ID NOs: 261, 258); anti-HER2-PD1-SIGLEC10 (e.g., SEQ ID NOs: 249, 246); anti-EGFRvIII-PD1-SIGLEC10 (e.g., SEQ ID NOs: 237, 234).

In some embodiments, the fusion protein comprises PD1 ECD and a polypeptide that inhibits VEGF/VEGFR signaling. In some embodiments, the fusion protein comprises PD1 ECD and anti-VEGFR mAb with PD1 ECD fused to either the heavy chain or light chain of the antibody. In some embodiments, this fusion protein is anti-VEGFR-PD1 (e.g., SEQ ID NOs: 377, 148). In a further embodiment, the fusion protein may additionally comprise a receptor ECD fused to the other chain of the antibody. In some embodiments, the fusion protein is selected from anti-VEGFR-PD1-TIM3 (e.g., SEQ ID NOs: 377, 376); anti-VEGFR-PD1-BTLA (e.g., SEQ ID NOs: 377, 378); anti-VEGFR-PD1-SIRPa (e.g., SEQ ID NOs: 377, 375); anti-VEGFR-PD1-SIGLEC10 (e.g., SEQ ID NOs: 377, 374).

In some embodiments, the fusion protein comprises PD1 ECD and anti-VEGF mAb with PD1 ECD fused to either the heavy chain or light chain of the antibody. In some embodiments, this fusion protein is anti-VEGF-PD1 (e.g., SEQ ID NOs: 366, 32). In a further embodiment, the fusion protein may additionally comprise a receptor ECD fused to the other chain of the antibody. In some embodiments, the fusion protein is selected from anti-VEGF-PD1-BTLA (e.g., SEQ ID NOs: 366, 367); anti-VEGF-PD1-TIM3 (e.g., SEQ ID NOs: 366, 365); anti-VEGF-PD1-SIRPa (e.g., SEQ ID NOs: 366, 364); anti-VEGF-PD1-SIGLEC10 (e.g., SEQ ID NOs: 366, 363).

In other embodiments, the fusion protein comprises PD1 ECD and VEGFR ECD. In one embodiment, this fusion protein is PD1-Fc-VEGFR (e.g., SEQ ID NO: 540). In another embodiment, this fusion protein is VEGFR-Fc-PD1 (e.g., SEQ ID NO: 566)

In some embodiments, the fusion protein comprises an antibody that binds IL-17 or IL-17R and PD1 ECD. In some embodiments, this fusion protein is selected from the following: anti-IL17-PD1, anti-IL17R-PD1 (e.g., SEQ ID NOs: 330, 63).

In a further embodiment, the fusion protein comprises an antibody that binds IL-17 or IL-17R, PD1 ECD, and an additional receptor ECD. In one embodiment, PD1 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, PD1 ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-IL17R-PD1-SIRPa (e.g., SEQ ID NOs: 330, 328). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL17R-PD1-SIGLEC10 (e.g., SEQ ID NOs: 330, 327).

In some embodiments, the fusion protein comprises an antibody that binds IL-23 or IL-23R and PD1 ECD. If the antibody binds IL-23, it is preferred that the antibody bind the p19 subunit of IL-23 that is not shared with IL-12. In some embodiments, this fusion protein is selected from the following: anti-IL23-PD1 (e.g., SEQ ID NOs: 342, 75), anti-IL23R-PD1.

In a further embodiment, the fusion protein comprises an antibody that binds IL-23 or IL-23R, PD1 ECD, and an additional receptor ECD. In one embodiment, PD1 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, PD1 ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-IL23-PD1-SIRPa (e.g., SEQ ID NOs: 342, 340). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL23-PD1-SIGLEC10 (e.g., SEQ ID NOs: 342, 339).

In some embodiments, the fusion protein comprises an antibody that binds IL-6 or IL-6R, PD1 ECD, and an additional receptor ECD. In one embodiment, PD1 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, PD1 ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-IL6R-PD1-SIRPa (e.g., SEQ ID NOs: 318, 316). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL6R-PD1-SIGLEC10 (e.g., SEQ ID NOs: 318, 315).

In some embodiments, the fusion protein further comprises an additional receptor ECD. Exemplary embodiments of this fusion protein include anti-TGFb-PD1-SIRPa (e.g., SEQ ID NOs: 398, 396); anti-TGFb-PD1-BTLA (e.g., SEQ ID NOs: 398, 399); anti-TGFb-PD1-SIGLEC10 (e.g., SEQ ID NOs: 398, 395); anti-TGFb-PD1-TIM3 (e.g., SEQ ID NOs: 398, 397).

In some embodiments, the fusion protein comprises PD1 ECD and IL-15. In some embodiments, the fusion protein is IL15-Fc-PD1 (e.g., SEQ ID NO: 578) or PD1-Fc-IL15 (e.g., SEQ ID NO: 577). In other embodiments, the fusion protein is IL12-Fc-PD1 (e.g., SEQ ID NO: 576) or PD1-Fc-IL12 (e.g., SEQ ID NO: 575). In other embodiments, the fusion protein comprises an antibody with PD1 ECD fused to heavy chain and IL-15 fused to light chain. In other embodiments, the fusion protein comprises an antibody with PD1 ECD fused to heavy chain and IL-12 fused to light chain.

In various embodiments, the fusion proteins of the invention counteract TIM-3/CEACAM in the tumor microenvironment. In some embodiments, the fusion proteins comprise a ligand-binding sequence of an extracellular domain of TIM-3 (e.g., TIM-3 ECD).

In one embodiment, the fusion protein is an ALT that comprises an antibody that binds TIM3 or a TIM3 ligand (e.g. CEACAM1). In one example, the ALT comprises an antibody that binds TIM3 and interferes with its interaction with CEACAM1. In one example, the ALT comprises an antibody that binds CEACAM and interferes with its heterodimerization with TIM3 or homodimerization with CEACAM. In one aspect, the antibody is an antagonist that inhibits TIM3/TIM3 ligand interaction or intracellular ITIM or ITSM signaling, thereby promoting immune cell activation. In various examples, the antibody that binds TIM3 or CEACAM is fused to one or more ligand traps. In one example the TIM3 or CEACAM antibody is fused to a ligand-binding sequence of the extracellular domain of PD1 (PD1 ECD). In one example the TIM3 or CEACAM antibody is fused to a ligand-binding sequence of the extracellular domain of TGFbR (TGFbRII ECD). In one example the TIM3 or CEACAM antibody is fused to a ligand-binding sequence of the extracellular domain of BTLA (BTLA ECD). In one example the TIM3 or CEACAM antibody is fused to a ligand-binding sequence of the extracellular domain of SIRPa (SIRPa ECD). In one example the TIM3 or CEACAM antibody is fused to a ligand-binding sequence of the extracellular domain of VEGFR (VEGFR ECD). In one embodiment, the TIM3 or CEACAM binding antibody is fused to multiple ligand traps selected from the following: PD1 ECD, TGFbRII ECD, BTLA ECD, SIRPa ECD, VEGFR ECD, SIGLEC10 ECD. In one aspect, a ligand trap is fused to the heavy chain, and a second ligand trap is fused to the light chain.

In various examples, the ALT comprises a TIM3 or CEACAM binding antibody, wherein the heavy chain is fused to TGFbRII ECD and the light chain is fused to PD1 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD. In various examples, the ALT comprises a TIM3 or CEACAM binding antibody, wherein the heavy chain is fused to VEGFR ECD and the light chain is fused to PD1 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD. In various examples, the ALT comprises a TIM3 or CEACAM binding antibody, wherein the heavy chain is fused to PD1 ECD and the light chain is fused to BTLA ECD, SIRPa ECD, or SIGLEC10 ECD. In various examples, the ALT comprises a TIM3 or CEACAM binding antibody, wherein the heavy chain is fused to BTLA ECD and the light chain is fused to PD1 ECD, SIRPa ECD, or SIGLEC10 ECD. In various examples, the ALT comprises a TIM3 or CEACAM binding antibody, wherein the heavy chain is fused to SIRPa ECD and the light chain is fused to BTLA ECD, PD1 ECD, or SIGLEC10 ECD. In various examples, the ALT comprises a TIM3 or CEACAM binding antibody, wherein the heavy chain is fused to SIGLEC10 ECD and the light chain is fused to BTLA ECD, SIRPa ECD, or PD1 ECD.

In one embodiment, the fusion proteins of the invention comprise a ligand-binding sequence of an extracellular domain of TIM-3 (TIM3 ECD) to bind and disable TIM-3 ligands (CEACAM1, CEACAM5).

In some embodiments, the fusion protein of the invention comprises a targeting polypeptide that is an antibody. In one embodiment, the antibody is fused to TIM3 ECD and additional ligand traps selected from the following: PD1 ECD, TGFbRII ECD, BTLA ECD, SIRPa ECD, VEGFR ECD, SIGLEC10 ECD. In one aspect, a ligand trap (LT1) is fused to the heavy chain, and a second ligand trap (LT2) is fused to the light chain. In one aspect, the TIM3 ECD is fused to the heavy chain and another ligand trap is fused to the light chain. In one aspect, the TIM3 ECD is fused to the light chain and another ligand trap is fused to the heavy chain. In various examples, the ALT comprises an antibody, wherein the heavy chain is fused to TIM3 ECD and the light chain is fused to one of PD1 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD. In various examples, the ALT comprises an antibody wherein the light chain is fused to TIM3 ECD and the heavy chain is fused to one of PD1 ECD, TGFbRII ECD, BTLA ECD, SIRPa ECD, VEGFR ECD, SIGLEC10 ECD.

In some embodiments, the fusion protein comprises TIM3 ECD and a polypeptide that inhibits the interaction between CD47 and SIRPa. In one embodiment, this fusion protein comprises TIM3 ECD and a polypeptide that binds CD47. In one embodiment, this fusion protein is anti-CD47 mAb fused to TIM3 ECD (anti-CD47-TIM3 (e.g., SEQ ID NOs: 391, 22)). In another embodiment, this fusion protein comprises SIRPa ECD and TIM3 ECD. In one embodiment, this fusion protein is SIRPa-Fc-TIM3 (e.g., SEQ ID NO: 551) or TIM3-Fc-SIRPa (e.g., SEQ ID NO: 562).

In a further aspect, the fusion protein comprises TIM3 ECD, a polypeptide that inhibits the interaction between CD47 and SIRPa, and another polypeptide that inhibits a T cell co-inhibitory molecule. In some embodiments, this fusion protein comprises anti-CD47 mAb with TIM3 ECD fused to the heavy chain or light chain; and a T cell co-inhibitory molecule ECD fused to the other chain. In a particular embodiment, this fusion protein is anti-CD47-TIM3-PD1 (e.g., SEQ ID NOs: 391, 384).

In another aspect, the fusion protein comprises TIM3 ECD, SIRPa ECD, and an antibody with a heavy chain and light chain. In one aspect, the TIM3 ECD is fused to the heavy chain of the antibody and the SIRPa ECD is fused to the light chain of the antibody. In another aspect, the TIM3 ECD is fused to the light chain of the antibody and the SIRPa ECD is fused to the heavy chain of the antibody. In some embodiments, the antibody of said fusion protein binds a T cell co-inhibitory molecule as an antagonist. Exemplary embodiments of such fusion proteins include anti-CTLA4-TIM3-SIRPa (e.g., SEQ ID NOs: 445, 438), anti-PD1-TIM3-SIRPa (e.g., SEQ ID NOs: 457, 450), and anti-PDL1-TIM3-SIRPa (e.g., SEQ ID NOs: 467, 461). In other embodiments, the antibody of said fusion protein binds a T cell co-stimulatory molecule as an agonist. Exemplary embodiments of this fusion protein include anti-OX40-TIM3-SIRPa (e.g., SEQ ID NOs: 515, 508), anti-41BB-TIM3-SIRPa (e.g., SEQ ID NOs: 503, 496), and anti-CD40-TIM3-SIRPa. In other embodiments, the antibody of said fusion protein is a tumor-targeted antibody. In some embodiments, this tumor targeted-antibody binds a tumor growth factor or growth factor receptor. In other embodiments, this tumor targeted antibody binds a tumor cell surface molecule. Exemplary embodiments of this fusion protein include anti-EGFR-TIM3-SIRPa (e.g., SEQ ID NOs: 230, 223), anti-HER2-TIM3-SIRPa (e.g., SEQ ID NOs: 254, 247), anti-EGFRvIII-TIM3-SIRPa (e.g., SEQ ID NOs: 242, 235), anti-uPAR-TIM3-SIRPa, and anti-PSMA-TIM3-SIRPa.

In other embodiments, the antibody of said fusion protein binds a member of the TGFb pathway. In some embodiments, this antibody binds TGFb, TGFbR, or GARP.

Exemplary embodiments of this fusion protein include anti-TGFb-TIM3-SIRPa (e.g., SEQ ID NOs: 402, 396), anti-TGFbR-TIM3-SIRPa, and anti-GARP-TIM3-SIRPa.

In other embodiments, the antibody of said fusion protein binds VEGF or VEGFR. Exemplary embodiments of this fusion protein include anti-VEGF-TIM3-SIRPa (e.g., SEQ ID NOs: 371, 364) and anti-VEGFR-TIM3-SIRPa (e.g., SEQ ID NOs: 382, 375).

In some embodiments, the fusion protein comprises TIM3 ECD and a polypeptide that inhibits the interaction of TIGIT or PVRIG with PVRL2 or PVR. In some embodiments, this fusion protein comprises an antibody that binds TIGIT or PVRIG fused to TIM3 ECD. Exemplary embodiments of this fusion protein include anti-TIGIT-TIM3 (e.g., SEQ ID NOs: 479, 139) and anti-PVRIG-TIM3.

In some embodiments, the fusion protein comprises TIM3 ECD and a polypeptide that inhibits the interaction of VISTA and VSIG8. In some embodiments, this fusion protein comprises an antibody that binds VISTA or VSIG8 fused to TIM3 ECD. Exemplary embodiments of this fusion protein include anti-VISTA-TIM3 and anti-VSIG8-TIM3.

In some embodiments, the fusion protein comprises TIM3 ECD and a polypeptide that inhibits the interaction of PD-1 and PD-L1. In some embodiments, this fusion protein comprises an antibody that binds PD-1 or PD-L1 fused to TIM3 ECD. Exemplary embodiments of this fusion protein include anti-PD1-TIM3 (e.g., SEQ ID NOs: 457, 101) and anti-PDL1-TIM3 (e.g., SEQ ID NOs: 467, 109).

In some embodiments, the fusion protein comprises TIM3 ECD and a polypeptide that inhibits CTLA-4. In some embodiments, this fusion protein comprises an antibody that binds CTLA-4 fused to TIM3 ECD. Exemplary embodiments of this fusion protein include anti-CTLA4-TIM3 (e.g., SEQ ID NOs: 445, 28).

In some embodiments, the fusion protein comprises TIM3 ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and an additional receptor ECD. In one aspect, the TIM3 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the TIM3 ECD is fused to the light chain and the additional receptor ECD is fused to the heavy chain.

In some embodiments, the fusion protein comprises TIM3 ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and PD1 ECD. Exemplary embodiments of this fusion protein include anti-CTLA4-TIM3-PD1 (e.g., SEQ ID NOs: 445, 436); anti-PD1-TIM3-PD1 (e.g., SEQ ID NOs: 457, 448); anti-TIGIT-TIM3-PD1 (e.g., SEQ ID NOs: 479, 470); anti-TIM3-TIM3-PD1 (e.g., SEQ ID NOs: 491, 482).

In other embodiments, the fusion protein comprises TIM3 ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and SIRPa ECD. Exemplary embodiments of this fusion protein include anti-PD1-TIM3-SIRPa (e.g., SEQ ID NOs: 457, 450); anti-PDL1-TIM3-SIRPa (e.g., SEQ ID NOs: 467, 461); anti-TIGIT-TIM3-SIRPa (e.g., SEQ ID NOs: 479, 472); anti-CTLA4-TIM3-SIRPa (e.g., SEQ ID NOs: 445, 438); anti-TIM3-TIM3-SIRPa (e.g., SEQ ID NOs: 491, 484).

In other embodiments, the fusion protein comprises TIM3 ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and SIGLEC10 ECD. Exemplary embodiments of this fusion protein include anti-TIGIT-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 479, 471); anti-TIM3-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 491, 483); anti-PDL1-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 467, 460); anti-CTLA4-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 445, 437); anti-PD1-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 457, 449).

In other embodiments, the fusion protein comprises TIM3 ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and VEGFR ECD. Exemplary embodiments of this fusion protein include anti-PDL1-VEGFR-TIM3 (e.g., SEQ ID NOs: 468, 462); anti-CTLA4-VEGFR-TIM3 (e.g., SEQ ID NOs: 446, 439); anti-TIM3-VEGFR-TIM3 (e.g., SEQ ID NOs: 492, 485); anti-PD1-VEGFR-TIM3 (e.g., SEQ ID NOs: 458, 451); anti-TIGIT-VEGFR-TIM3 (e.g., SEQ ID NOs: 480, 473)

In a further aspect, the fusion protein comprises an antibody that binds a T cell-costimulatory molecule, TIM3 ECD, and an additional receptor ECD. In one aspect, the TIM3 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the TIM3 ECD is fused to the light chain of the antibody and the additional receptor ECD is fused to the heavy chain of the antibody. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-ICOS-TIM3-PD1 (e.g., SEQ ID NOs: 527, 518); anti-41BB-TIM3-PD1 (e.g., SEQ ID NOs: 503, 494); anti-OX40-TIM3-PD1 (e.g., SEQ ID NOs: 515, 506). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-41BB-TIM3-SIRPa (e.g., SEQ ID NOs: 503, 496); anti-ICOS-TIM3-SIRPa (e.g., SEQ ID NOs: 527, 520); anti-OX40-TIM3-SIRPa (e.g., SEQ ID NOs: 515, 508). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-ICOS-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 527, 519); anti-41BB-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 503, 495); anti-OX40-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 515, 507).

In some embodiments, the fusion protein comprises an antibody, TIM3 ECD, and the ECD of a T cell co-stimulatory molecule. In one aspect, the TIM3 ECD is fused to heavy chain and the ECD of a T cell co-stimulatory molecule fused to light chain. Alternatively, the TIM3 ECD is fused to the light chain and the T cell co-stimulatory molecule ECD is fused to the heavy chain. In some embodiments, the fusion protein comprises TIM3 ECD and one of the following: OX40L, 41BBL, ICOSL.

In one embodiment, the fusion protein comprises TIM3 ECD and a polypeptide that binds an ectonucleotidase. In a preferred embodiment, the ectonucleotidase is either CD39 or CD73. In some embodiments, the fusion protein is an antibody that binds CD39 or CD73 fused to TIM3 ECD; for example: anti-CD39-TIM3 (e.g., SEQ ID NOs: 433, 18) or anti-CD73-TIM3 (e.g., SEQ ID NOs: 426, 24).

In some embodiments, the fusion protein comprises TIM3 ECD, an antibody that binds CD39 or CD73, and an additional receptor ECD. In some embodiments, the TIM3 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the TIM3 ECD is fused to the light chain of the antibody and the additional receptor ECD is fused to the heavy chain of the antibody. In some embodiments, the fusion protein is selected from the following: anti-CD73-TIM3-SIRPa (e.g., SEQ ID NOs: 426, 419); anti-CD73-TIM3-PD1 (e.g., SEQ ID NOs: 426, 417).

In some embodiments, the fusion protein comprises a tumor-targeted antibody and TIM3 ECD. In some embodiments, this tumor targeted-antibody binds a tumor growth factor or growth factor receptor. In other embodiments, this tumor targeted antibody binds a tumor cell surface molecule. In some embodiments, this fusion protein is selected from the following: anti-EGFR-TIM3 (e.g., SEQ ID NOs: 230, 43), anti-HER2-TIM3 (e.g., SEQ ID NOs: 254, 55), anti-EGFRvIII-TIM3 (e.g., SEQ ID NOs: 242, 47), anti-uPAR-TIM3 (e.g., SEQ ID NOs: 273, 162), anti-PSMA-TIM3 (e.g., SEQ ID NOs: 280, 121), anti-nectin-4-TIM3.

In a further embodiment, the fusion protein comprises a tumor-targeted antibody, TIM3 ECD, and an additional receptor ECD. In one embodiment, the TIM3 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the TIM3 ECD is fused to the light chain and the additional receptor ECD is fused to the heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-HER2-TIM3-PD1 (e.g., SEQ ID NOs: 254, 245); anti-EGFR-TIM3-PD1 (e.g., SEQ ID NOs: 230, 221); anti-nectin4-TIM3-PD1 (e.g., SEQ ID NOs: 266, 257); anti-EGFRvIII-TIM3-PD1 (e.g., SEQ ID NOs: 242, 233). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-EGFR-TIM3-SIRPa (e.g., SEQ ID NOs: 230, 223); anti-nectin4-TIM3-SIRPa (e.g., SEQ ID NOs: 266, 259); anti-HER2-TIM3-SIRPa (e.g., SEQ ID NOs: 254, 247); anti-EGFRvIII-TIM3-SIRPa (e.g., SEQ ID NOs: 242, 235). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-HER2-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 254, 246); anti-nectin4-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 266, 258); anti-EGFR-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 230, 222); anti-EGFRvIII-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 242, 234). In another aspect, the additional receptor ECD is VEGFR ECD. In some embodiments, the fusion protein is selected from: anti-EGFR-VEGFR-TIM3 (e.g., SEQ ID NOs: 231, 224); anti-EGFRvIII-VEGFR-TIM3 (e.g., SEQ ID NOs: 243, 236); anti-HER2-VEGFR-TIM3 (e.g., SEQ ID NOs: 255, 248); anti-nectin4-VEGFR-TIM3 (e.g., SEQ ID NOs: 267, 260).

In some embodiments, the fusion protein comprises TIM3 ECD and a polypeptide that inhibits VEGF/VEGFR signaling.

In some embodiments, the fusion protein comprises TIM3 ECD and anti-VEGFR mAb with TIM3 ECD fused to either the heavy chain or light chain of the antibody. In some embodiments, this fusion protein is anti-VEGFR-TIM3 (e.g., SEQ ID NOs: 382, 148). In a further embodiment, the fusion protein may additionally comprise a receptor ECD fused to the other chain of the antibody. In some embodiments, the fusion protein is selected from anti-VEGFR-TIM3-BTLA (e.g., SEQ ID NOs: 382, 378); anti-VEGFR-TIM3-SIRPa (e.g., SEQ ID NOs: 382, 375); anti-VEGFR-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 382, 374); anti-VEGFR-TIM3-PD1 (e.g., SEQ ID NOs: 382, 373).

In some embodiments, the fusion protein comprises TIM3 ECD and anti-VEGF mAb with TIM3 ECD fused to either the heavy chain or light chain of the antibody. In some embodiments, this fusion protein is anti-VEGF-TIM3 (e.g., SEQ ID NOs: 371, 32). In a further embodiment, the fusion protein may additionally comprise a receptor ECD fused to the other chain of the antibody. In some embodiments, the fusion protein is selected from anti-VEGF-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 371, 363); anti-VEGF-TIM3-BTLA (e.g., SEQ ID NOs: 371, 367); anti-VEGF-TIM3-PD1 (e.g., SEQ ID NOs: 371, 362); anti-VEGF-TIM3-SIRPa (e.g., SEQ ID NOs: 371, 364).

In other embodiments, the fusion protein comprises TIM3 ECD and VEGFR ECD. In one embodiment, this fusion protein is TIM3-Fc-VEGFR (e.g., SEQ ID NO: 564). In another embodiment, this fusion protein is VEGFR-Fc-TIM3 (e.g., SEQ ID NO: 570).

In some embodiments, the fusion protein comprises an antibody that binds IL-17 or IL-17R and TIM3 ECD. In some embodiments, this fusion protein is selected from the following: anti-IL17-TIM3, anti-IL17R-TIM3 (e.g., SEQ ID NOs: 335, 63).

In a further embodiment, the fusion protein comprises an antibody that binds IL-17 or IL-17R, TIM3 ECD, and an additional receptor ECD. In one embodiment, TIM3 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, TIM3 ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-IL17R-TIM3-PD1 (e.g., SEQ ID NOs: 335, 326). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-IL17R-TIM3-SIRPa (e.g., SEQ ID NOs: 335, 328). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL17R-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 335, 327). In another aspect, the additional receptor ECD is VEGFR ECD. In some embodiments, the fusion protein is selected from: anti-IL6R-VEGFR-TIM3 (e.g., SEQ ID NOs: 324, 317).

In some embodiments, the fusion protein comprises an antibody that binds IL-23 or IL-23R and TIM3 ECD. If the antibody binds IL-23, it is preferred that the antibody bind the p19 subunit of IL-23 that is not shared with IL-12. In some embodiments, this fusion protein is selected from the following: anti-IL23-TIM3 (e.g., SEQ ID NOs: 347, 75), anti-IL23R-TIM3.

In a further embodiment, the fusion protein comprises an antibody that binds IL-23 or IL-23R, TIM3 ECD, and an additional receptor ECD. In one embodiment, TIM3 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, TIM3 ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-IL23-TIM3-PD1 (e.g., SEQ ID NOs: 347, 338). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-IL23-TIM3-SIRPa (e.g., SEQ ID NOs: 347, 340). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL23-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 347, 339). In another aspect, the additional receptor ECD is VEGFR ECD. In some embodiments, the fusion protein is selected from: anti-IL23-VEGFR-TIM3 (e.g., SEQ ID NOs: 348, 341).

In some embodiments, the fusion protein comprises an antibody that binds IL-6 or IL-6R and TIM3 ECD. In some embodiments, this fusion protein is selected from the following: anti-IL6-TIM3, anti-IL6R-TIM3 (e.g., SEQ ID NOs: 323, 79).

In some embodiments, the fusion protein comprises an antibody that binds IL-6 or IL-6R, TIM3 ECD, and an additional receptor ECD. In one embodiment, TIM3 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, TIM3 ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-IL6R-TIM3-PD1 (e.g., SEQ ID NOs: 323, 314). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-IL6R-TIM3-SIRPa (e.g., SEQ ID NOs: 323, 316). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL6R-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 323, 315). In another aspect, the additional receptor ECD is VEGFR ECD. In some embodiments, the fusion protein is selected from: anti-IL6R-VEGFR-TIM3 (e.g., SEQ ID NOs: 324, 317).

In some embodiments, the fusion protein further comprises an additional receptor ECD. Exemplary embodiments of this fusion protein include anti-TGFb-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 402, 395); anti-TGFb-TIM3-BTLA (e.g., SEQ ID NOs: 402, 399); anti-TGFb-TIM3-PD1 (e.g., SEQ ID NOs: 402, 394); anti-TGFb-TIM3-SIRPa (e.g., SEQ ID NOs: 402, 396).

In some embodiments, the fusion protein comprises TIM3 ECD and IL-15. In some embodiments, the fusion protein is IL15-Fc-TIM3 (e.g., SEQ ID NO: 594) or TIM3-Fc-IL15 (e.g., SEQ ID NO: 593). In other embodiments, the fusion protein is IL12-Fc-TIM3 (e.g., SEQ ID NO: 592) or TIM3-Fc-IL12 (e.g., SEQ ID NO: 591). In other embodiments, the fusion protein comprises an antibody with TIM3 ECD fused to heavy chain and IL-15 fused to light chain. In other embodiments, the fusion protein comprises an antibody with TIM3 ECD fused to heavy chain and IL-12 fused to light chain.

In various embodiments, the fusion proteins of the invention counteract BTLA/HVEM in the tumor microenvironment. In some embodiments, the fusion proteins comprise a ligand-binding sequence of an extracellular domain of BTLA (e.g., BTLA ECD).

In one embodiment, the fusion protein of the invention is an ALT comprising an antibody that binds BTLA or BTLA ligand (e.g. HVEM). In one example, the ALT comprises an antibody that binds BTLA and interferes with its interaction with HVEM. In one example, the ALT comprises an antibody that binds HVEM and interferes with its interaction with BTLA. In one aspect, the antibody is an antagonist that inhibits BTLA intracellular ITIM or ITSM signaling, thereby promoting immune cell activation. In various examples, the antibody that binds BTLA or HVEM is fused to one or more ligand traps. In one example the BTLA or HVEM antibody is fused to a ligand-binding sequence of the extracellular domain of PD1 (PD1 ECD). In one example the BTLA or HVEM antibody is fused to a ligand-binding sequence of the extracellular domain of TGFbR (TGFbRII ECD). In one example the BTLA or HVEM antibody is fused to a ligand-binding sequence of the extracellular domain of TIM3 (TIM3 ECD). In one example the BTLA or HVEM antibody is fused to a ligand-binding sequence of the extracellular domain of SIRPa (SIRPa ECD). In one example the BTLA or HVEM antibody is fused to a ligand-binding sequence of the extracellular domain of VEGFR (VEGFR ECD). In one embodiment, the BTLA or HVEM binding antibody is fused to multiple ligand traps selected from the following: PD1 ECD, TGFbRII ECD, TIM3 ECD, SIRPa ECD, VEGFR ECD. In one aspect, a ligand trap (LT1) is fused to the heavy chain, and a second ligand trap (LT2) is fused to the light chain.

In various examples, the ALT comprises a BTLA or HVEM binding antibody, wherein the heavy chain is fused to TGFbRII ECD and the light chain is fused to PD1 ECD, TIM3 ECD, SIRPa ECD, or SIGLEC10 ECD. In various examples, the ALT comprises a BTLA or HVEM binding antibody, wherein the heavy chain is fused to VEGFR ECD and the light chain is fused to PD1 ECD, TIM3 ECD, SIRPa ECD, or SIGLEC10 ECD. In various examples, the ALT comprises a BTLA or HVEM binding antibody, wherein the heavy chain is fused to PD1 ECD and the light chain is fused to TIM3 ECD, SIRPa ECD, or SIGLEC10 ECD. In various examples, the ALT comprises a BTLA or HVEM binding antibody, wherein the heavy chain is fused to TIM3 ECD and the light chain is fused to PD1 ECD, SIRPa ECD, or SIGLEC10 ECD. In various examples, the ALT comprises a BTLA or HVEM binding antibody, wherein the heavy chain is fused to SIRPa ECD and the light chain is fused to TIM3 ECD, PD1 ECD, or SIGLEC10 ECD. In various examples, the ALT comprises a BTLA or HVEM binding antibody, wherein the heavy chain is fused to SIGLEC10 ECD and the light chain is fused to TIM3 ECD, SIRPa ECD, or PD1 ECD. In another embodiment, the molecule contains a ligand-binding sequence of the extracellular domain of TIM3 (TIM3 ECD). In one aspect, the TIM3 ECD binds and disables TIM3 ligands (e.g. CEACAM1). In one aspect, the TIM3 ECD interferes with the interaction of TIM3 with CEACAM1 or homodimerization of CEACAM1.

In one embodiment, the fusion protein comprises a ligand-binding sequence of an extracellular domain of B- and T-lymphocyte attenuator (BTLA ECD). In some embodiments, the fusion protein comprises an antibody and BTLA ECD. In one embodiment, the BTLA ECD is fused to the heavy chain of the antibody. In another embodiment, the BTLA ECD is fused to the light chain of the antibody.

In some embodiments, the fusion protein of the invention comprises a targeting polypeptide that is an antibody. In one embodiment, the antibody is fused to BTLA ECD and additional ligand traps selected from the following: PD1 ECD, TGFbRII ECD, TIM3 ECD, SIRPa ECD, VEGFR ECD, SIGLEC10 ECD. In one aspect, a ligand trap (LT1) is fused to the heavy chain, and a second ligand trap (LT2) is fused to the light chain. In one aspect, the BTLA ECD is fused to the heavy chain and another ligand trap is fused to the light chain. In one aspect, the BTLA ECD is fused to the light chain and another ligand trap is fused to the heavy chain. In various examples, the ALT comprises an antibody, wherein the heavy chain is fused to TIM3 ECD and the light chain is fused to one of PD1 ECD, TIM3 ECD, SIRPa ECD, or SIGLEC10 ECD. In various examples, the ALT comprises an antibody wherein the light chain is fused to TIM3 ECD and the heavy chain is fused to one of PD1 ECD, TGFbRII ECD, TIM3 ECD, SIRPa ECD, VEGFR ECD, SIGLEC10 ECD.

In some embodiments, the fusion protein comprises BTLA ECD and a polypeptide that inhibits the interaction between CD47 and SIRPa. In one embodiment, this fusion protein comprises BTLA ECD and a polypeptide that binds CD47. In one embodiment, this fusion protein is anti-CD47 mAb fused to BTLA ECD (anti-CD47-BTLA (e.g., SEQ ID NOs: 383, 22)). In another embodiment, this fusion protein comprises SIRPa ECD and BTLA ECD. In one embodiment, this fusion protein is SIRPa-Fc-BTLA (e.g., SEQ ID NO: 547) or BTLA-Fc-SIRPa (e.g., SEQ ID NO: 531).

In a further aspect, the fusion protein comprises BTLA ECD, a polypeptide that inhibits the interaction between CD47 and SIRPa, and another polypeptide that inhibits a T cell co-inhibitory molecule. In some embodiments, this fusion protein comprises anti-CD47 mAb with BTLA ECD fused to the heavy chain or light chain; and a T cell co-inhibitory molecule ECD fused to the other chain. In a particular embodiment, this fusion protein is anti-CD47-BTLA-PD1 (e.g., SEQ ID NOs: 383, 384). In another embodiment, this fusion protein is anti-CD47-BTLA-TIM3 (e.g., SEQ ID NOs: 383, 386).

In another aspect, the fusion protein comprises BTLA ECD, SIRPa ECD, and an antibody with a heavy chain and light chain. In one aspect, the BTLA ECD is fused to the heavy chain of the antibody and the SIRPa ECD is fused to the light chain of the antibody. In another aspect, the BTLA ECD is fused to the light chain of the antibody and the SIRPa ECD is fused to the heavy chain of the antibody. In some embodiments, the antibody of said fusion protein binds a T cell co-inhibitory molecule as an antagonist. Exemplary embodiments of such fusion proteins include anti-CTLA4-BTLA-SIRPa (e.g., SEQ ID NOs: 435, 438), anti-PD1-BTLA-SIRPa (e.g., SEQ ID NOs: 447, 450), and anti-PDL1-BTLA-SIRPa (e.g., SEQ ID NOs: 459, 461). In other embodiments, the antibody of said fusion protein binds a T cell co-stimulatory molecule as an agonist. Exemplary embodiments of this fusion protein include anti-OX40-BTLA-SIRPa (e.g., SEQ ID NOs: 505, 508), anti-41BB-BTLA-SIRPa (e.g., SEQ ID NOs: 493, 496), and anti-CD40-BTLA-SIRPa. In other embodiments, the antibody of said fusion protein is a tumor-targeted antibody. In some embodiments, this tumor targeted-antibody binds a tumor growth factor or growth factor receptor. In other embodiments, this tumor targeted antibody binds a tumor cell surface molecule. Exemplary embodiments of this fusion protein include anti-EGFR-BTLA-SIRPa (e.g., SEQ ID NOs: 220, 223), anti-HER2-BTLA-SIRPa (e.g., SEQ ID NOs: 244, 247), anti-EGFRvIII-BTLA-SIRPa (e.g., SEQ ID NOs: 232, 235), anti-uPAR-BTLA-SIRPa, and anti-PSMA-BTLA-SIRPa.

In other embodiments, the antibody of said fusion protein binds a member of the TGFb pathway. In some embodiments, this antibody binds TGFb, TGFbR, or GARP. Exemplary embodiments of this fusion protein include anti-TGFb-BTLA-SIRPa (e.g., SEQ ID NOs: 393, 396), anti-TGFbR-BTLA-SIRPa, and anti-GARP-BTLA-SIRPa.

In other embodiments, the antibody of said fusion protein binds VEGF or VEGFR. Exemplary embodiments of this fusion protein include anti-VEGF-BTLA-SIRPa (e.g., SEQ ID NOs: 361, 364) and anti-VEGFR-BTLA-SIRPa (e.g., SEQ ID NOs: 372, 375).

In some embodiments, the fusion protein comprises BTLA ECD and a polypeptide that inhibits the interaction of TIGIT or PVRIG with PVRL2 or PVR. In some embodiments, this fusion protein comprises an antibody that binds TIGIT or PVRIG fused to BTLA ECD. Exemplary embodiments of this fusion protein include anti-TIGIT-BTLA (e.g., SEQ ID NOs: 469, 139) and anti-PVRIG-BTLA.

In some embodiments, the fusion protein comprises BTLA ECD and a polypeptide that inhibits the interaction of VISTA and VSIG8. In some embodiments, this fusion protein comprises an antibody that binds VISTA or VSIG8 fused to BTLA ECD. Exemplary embodiments of this fusion protein include anti-VISTA-BTLA and anti-VSIG8-BTLA.

In some embodiments, the fusion protein comprises BTLA ECD and a polypeptide that inhibits the interaction of PD-1 and PD-L1. In some embodiments, this fusion protein comprises an antibody that binds PD-1 or PD-L1 fused to BTLA ECD. Exemplary embodiments of this fusion protein include anti-PD1-BTLA (e.g., SEQ ID NOs: 447, 101) and anti-PDL1-BTLA (e.g., SEQ ID NOs: 459, 109) and anti-PDL1-TGFbRII-BTLA (e.g., SEQ ID NOs: 466, 464). In other embodiments, the polypeptide that inhibits the interaction of PD-1/PD-L1 is PD1 ECD. In one aspect, the fusion protein comprises Fc, BTLA ECD, and PD-1 ECD; and has the structure N-BTLA ECD-Fc-PD1 ECD-C, or N-PD1 ECD-Fc-BTLA ECD.

In some embodiments, the fusion protein comprises BTLA ECD and a polypeptide that inhibits CTLA-4. In some embodiments, this fusion protein comprises an antibody that binds CTLA-4 fused to BTLA ECD. Exemplary embodiments of this fusion protein include anti-CTLA4-BTLA (e.g., SEQ ID NOs: 435, 28).

In some embodiments, the fusion protein comprises BTLA ECD and a polypeptide that inhibits TIM-3. In some embodiments, this fusion protein comprises an antibody that binds TIM-3 fused to BTLA ECD. Exemplary embodiments of this fusion protein include anti-TIM3-BTLA (e.g., SEQ ID NOs: 481, 141).

In some embodiments, the fusion protein comprises BTLA ECD and a polypeptide that binds CEACAM1 and/or CEACAM5. In some embodiments, this fusion protein comprises an antibody that binds CEACAM1 or CEACAM5 fused to BTLA ECD. Exemplary embodiments of this fusion protein include anti-CEACAM5-BTLA (e.g., SEQ ID NOs: 282, 26). In other embodiments, this CEACAM-binding polypeptide is TIM3 ECD.

Fusion proteins comprising BTLA ECD and mAb that inhibits a T cell co-inhibitory molecule and additional receptor ECD

In some embodiments, the fusion protein comprises BTLA ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and an additional receptor ECD. In one aspect, the BTLA ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the BTLA ECD is fused to the light chain and the additional receptor ECD is fused to the heavy chain.

In some embodiments, the fusion protein comprises BTLA ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and PD1 ECD. In some embodiments, BTLA is fused to the light chain and PD-1 is fused to the heavy chain. In other embodiments, BTLA is fused to the heavy chain and PD-1 is fused to the light chain. Exemplary embodiments of this fusion protein include anti-PD1-BTLA-PD1 (e.g., SEQ ID NOs: 447, 448); anti-CTLA4-BTLA-PD1 (e.g., SEQ ID NOs: 435, 436); anti-TIGIT-BTLA-PD1 (e.g., SEQ ID NOs: 469, 470); anti-TIM3-BTLA-PD1 (e.g., SEQ ID NOs: 481, 482).

In other embodiments, the fusion protein comprises BTLA ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and TIM3 ECD. Exemplary embodiments of this fusion protein include anti-TIM3-BTLA-TIM3 (e.g., SEQ ID NOs: 481, 485); anti-CTLA4-BTLA-TIM3 (e.g., SEQ ID NOs: 435, 439); anti-TIGIT-BTLA-TIM3 (e.g., SEQ ID NOs: 469, 473); anti-PDL1-BTLA-TIM3 (e.g., SEQ ID NOs: 459, 462); anti-PD1-BTLA-TIM3 (e.g., SEQ ID NOs: 447, 451).

In other embodiments, the fusion protein comprises BTLA ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and SIRPa ECD. Exemplary embodiments of this fusion protein include anti-TIGIT-BTLA-SIRPa (e.g., SEQ ID NOs: 469, 472); anti-PDL1-BTLA-SIRPa (e.g., SEQ ID NOs: 459, 461); anti-CTLA4-BTLA-SIRPa (e.g., SEQ ID NOs: 435, 438); anti-TIM3-BTLA-SIRPa (e.g., SEQ ID NOs: 481, 484); anti-PD1-BTLA-SIRPa (e.g., SEQ ID NOs: 447, 450).

In other embodiments, the fusion protein comprises BTLA ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and SIGLEC10 ECD. Exemplary embodiments of this fusion protein include anti-CTLA4-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 435, 437); anti-TIM3-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 481, 483); anti-TIGIT-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 469, 471); anti-PD1-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 447, 449); anti-PDL1-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 459, 460).

In other embodiments, the fusion protein comprises BTLA ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and VEGFR ECD. Exemplary embodiments of this fusion protein include anti-TIGIT-VEGFR-BTLA (e.g., SEQ ID NOs: 480, 475); anti-TIM3-VEGFR-BTLA (e.g., SEQ ID NOs: 492, 487); anti-PDL1-VEGFR-BTLA (e.g., SEQ ID NOs: 468, 464); anti-PD1-VEGFR-BTLA (e.g., SEQ ID NOs: 458, 453); anti-CTLA4-VEGFR-BTLA (e.g., SEQ ID NOs: 446, 441).

In a further aspect, the fusion protein comprises an antibody that binds a T cell-costimulatory molecule, BTLA ECD, and an additional receptor ECD. In one aspect, the BTLA ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the BTLA ECD is fused to the light chain of the antibody and the additional receptor ECD is fused to the heavy chain of the antibody. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-OX40-BTLA-PD1 (e.g., SEQ ID NOs: 505, 506); anti-ICOS-BTLA-PD1 (e.g., SEQ ID NOs: 517, 518); anti-41BB-BTLA-PD1 (e.g., SEQ ID NOs: 493, 494). In another embodiment, the T cell co-inhibitory molecule is TIM3. In some embodiments, the fusion protein is selected from: anti-ICOS-BTLA-TIM3 (e.g., SEQ ID NOs: 517, 521); anti-41BB-BTLA-TIM3 (e.g., SEQ ID NOs: 493, 497); anti-OX40-BTLA-TIM3 (e.g., SEQ ID NOs: 505, 509). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-ICOS-BTLA-SIRPa (e.g., SEQ ID NOs: 517, 520); anti-OX40-BTLA-SIRPa (e.g., SEQ ID NOs: 505, 508); anti-41BB-BTLA-SIRPa (e.g., SEQ ID NOs: 493, 496). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-41BB-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 493, 495); anti-ICOS-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 517, 519); anti-OX40-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 505, 507).

Fusion proteins comprising BTLA ECD and mAb and T cell co-stimulatory ECD

In some embodiments, the fusion protein comprises an antibody, BTLA ECD, and the ECD of a T cell co-stimulatory molecule. In one aspect, the BTLA ECD is fused to heavy chain and the ECD of a T cell co-stimulatory molecule fused to light chain. Alternatively, the BTLA ECD is fused to the light chain and the T cell co-stimulatory molecule ECD is fused to the heavy chain. In some embodiments, the fusion protein comprises BTLA ECD and one of the following: OX40L, 41BBL, ICOSL.

In one embodiment, the fusion protein comprises BTLA ECD and a polypeptide that binds an ectonucleotidase. In a preferred embodiment, the ectonucleotidase is either CD39 or CD73. In some embodiments, the fusion protein is an antibody that binds CD39 or CD73 fused to BTLA ECD; for example: anti-CD39-BTLA (e.g., SEQ ID NOs: 428, 18) or anti-CD73-BTLA (e.g., SEQ ID NOs: 416, 24).

In some embodiments, the fusion protein comprises BTLA ECD, an antibody that binds CD39 or CD73, and an additional receptor ECD. In some embodiments, the BTLA ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the BTLA ECD is fused to the light chain of the antibody and the additional receptor ECD is fused to the heavy chain of the antibody. In some embodiments, the fusion protein is selected from the following: anti-CD73-BTLA-SIRPa (e.g., SEQ ID NOs: 416, 419); anti-CD73-BTLA-TIM3 (e.g., SEQ ID NOs: 416, 420); anti-CD73-BTLA-PD1 (e.g., SEQ ID NOs: 416, 417).

In some embodiments, the fusion protein comprises a tumor-targeted antibody and BTLA ECD. In some embodiments, this tumor targeted-antibody binds a tumor growth factor or growth factor receptor. In other embodiments, this tumor targeted antibody binds a tumor cell surface molecule. In some embodiments, this fusion protein is selected from the following: anti-EGFR-BTLA (e.g., SEQ ID NOs: 220, 43), anti-HER2-BTLA (e.g., SEQ ID NOs: 244, 55), anti-EGFRvIII-BTLA (e.g., SEQ ID NOs: 232, 47), anti-uPAR-BTLA (e.g., SEQ ID NOs: 268, 162), anti-PSMA-BTLA (e.g., SEQ ID NOs: 275, 121), anti-nectin-4-BTLA.

In a further embodiment, the fusion protein comprises a tumor-targeted antibody, BTLA ECD, and an additional receptor ECD. In one embodiment, the BTLA ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the BTLA ECD is fused to the light chain and the additional receptor ECD is fused to the heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-HER2-BTLA-PD1 (e.g., SEQ ID NOs: 244, 245); anti-EGFR-BTLA-PD1 (e.g., SEQ ID NOs: 220, 221); anti-EGFRvIII-BTLA-PD1 (e.g., SEQ ID NOs: 232, 233); anti-nectin4-BTLA-PD1 (e.g., SEQ ID NOs: 256, 257). In another embodiment, the T cell co-inhibitory molecule is TIM3. In some embodiments, the fusion protein is selected from: anti-EGFRvIII-BTLA-TIM3 (e.g., SEQ ID NOs: 232, 236); anti-nectin4-BTLA-TIM3 (e.g., SEQ ID NOs: 256, 260); anti-EGFR-BTLA-TIM3 (e.g., SEQ ID NOs: 220, 224); anti-HER2-BTLA-TIM3 (e.g., SEQ ID NOs: 244, 248). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-EGFRvIII-BTLA-SIRPa (e.g., SEQ ID NOs: 232, 235); anti-nectin4-BTLA-SIRPa (e.g., SEQ ID NOs: 256, 259); anti-HER2-BTLA-SIRPa (e.g., SEQ ID NOs: 244, 247); anti-EGFR-BTLA-SIRPa (e.g., SEQ ID NOs: 220, 223). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-EGFR-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 220, 222); anti-nectin4-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 256, 258); anti-HER2-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 244, 246); anti-EGFRvIII-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 232, 234). In another aspect, the additional receptor ECD is VEGFR ECD. In some embodiments, the fusion protein is selected from: anti-nectin4-VEGFR-BTLA (e.g., SEQ ID NOs: 267, 262); anti-EGFR-VEGFR-BTLA (e.g., SEQ ID NOs: 231, 226); anti-HER2-VEGFR-BTLA (e.g., SEQ ID NOs: 255, 250); anti-EGFRvIII-VEGFR-BTLA (e.g., SEQ ID NOs: 243, 238).

In some embodiments, the fusion protein comprises BTLA ECD and a polypeptide that inhibits VEGF/VEGFR signaling.

In some embodiments, the fusion protein comprises BTLA ECD and anti-VEGFR mAb with BTLA ECD fused to either the heavy chain or light chain of the antibody. In some embodiments, this fusion protein is anti-VEGFR-BTLA (e.g., SEQ ID NOs: 372, 148). In a further embodiment, the fusion protein may additionally comprise a receptor ECD fused to the other chain of the antibody. In some embodiments, the fusion protein is selected from anti-VEGFR-BTLA-SIRPa (e.g., SEQ ID NOs: 372, 375); anti-VEGFR-BTLA-PD1 (e.g., SEQ ID NOs: 372, 373); anti-VEGFR-BTLA-TIM3 (e.g., SEQ ID NOs: 372, 376); anti-VEGFR-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 372, 374).

In some embodiments, the fusion protein comprises BTLA ECD and anti-VEGF mAb with BTLA ECD fused to either the heavy chain or light chain of the antibody. In some embodiments, this fusion protein is anti-VEGF-BTLA (e.g., SEQ ID NOs: 361, 32). In a further embodiment, the fusion protein may additionally comprise a receptor ECD fused to the other chain of the antibody. In some embodiments, the fusion protein is selected from anti-VEGF-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 361, 363); anti-VEGF-BTLA-SIRPa (e.g., SEQ ID NOs: 361, 364); anti-VEGF-BTLA-PD1 (e.g., SEQ ID NOs: 361, 362); anti-VEGF-BTLA-TIM3 (e.g., SEQ ID NOs: 361, 365).

In other embodiments, the fusion protein comprises BTLA ECD and VEGFR ECD. In one embodiment, this fusion protein is BTLA-Fc-VEGFR (e.g., SEQ ID NO: 534). In another embodiment, this fusion protein is VEGFR-Fc-BTLA (e.g., SEQ ID NO: 565).

In some embodiments, the fusion protein comprises an antibody that binds IL-17 or IL-17R and BTLA ECD. In some embodiments, this fusion protein is selected from the following: anti-IL17-BTLA, anti-IL17R-BTLA (e.g., SEQ ID NOs: 325, 63).

In a further embodiment, the fusion protein comprises an antibody that binds IL-17 or IL-17R, BTLA ECD, and an additional receptor ECD. In one embodiment, BTLA ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, BTLA ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-IL17R-BTLA-PD1 (e.g., SEQ ID NOs: 325, 326). In another embodiment, the T cell co-inhibitory molecule is TIM3. In some embodiments, the fusion protein is selected from: anti-IL17R-BTLA-TIM3 (e.g., SEQ ID NOs: 325, 329). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-IL17R-BTLA-SIRPa (e.g., SEQ ID NOs: 325, 328). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL17R-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 325, 327). In another aspect, the additional receptor ECD is VEGFR ECD. In some embodiments, the fusion protein is selected from: anti-IL6R-VEGFR-BTLA (e.g., SEQ ID NOs: 324, 319).

In some embodiments, the fusion protein comprises an antibody that binds IL-23 or IL-23R and BTLA ECD. If the antibody binds IL-23, it is preferred that the antibody bind the p19 subunit of IL-23 that is not shared with IL-12. In some embodiments, this fusion protein is selected from the following: anti-IL23-BTLA (e.g., SEQ ID NOs: 337, 75), anti-IL23R-BTLA.

In a further embodiment, the fusion protein comprises an antibody that binds IL-23 or IL-23R, BTLA ECD, and an additional receptor ECD. In one embodiment, BTLA ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, BTLA ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-IL23-BTLA-PD1 (e.g., SEQ ID NOs: 337, 338). In another embodiment, the T cell co-inhibitory molecule is TIM3. In some embodiments, the fusion protein is selected from: anti-IL23-BTLA-TIM3 (e.g., SEQ ID NOs: 337, 341). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-IL23-BTLA-SIRPa (e.g., SEQ ID NOs: 337, 340). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL23-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 337, 339). In another aspect, the additional receptor ECD is VEGFR ECD. In some embodiments, the fusion protein is selected from: anti-IL23-VEGFR-BTLA (e.g., SEQ ID NOs: 348, 343).

In some embodiments, the fusion protein comprises an antibody that binds IL-6 or IL-6R and BTLA ECD. In some embodiments, this fusion protein is selected from the following: anti-IL6-BTLA, anti-IL6R-BTLA (e.g., SEQ ID NOs: 313, 79).

In a further embodiment, the fusion protein comprises an antibody that binds IL-6 or IL-6R, BTLA ECD, and an additional receptor ECD. In one embodiment, BTLA ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, BTLA ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In one embodiment, the T cell co-inhibitory molecule is PD-1. In some embodiments, the fusion protein is selected from: anti-IL6R-BTLA-PD1 (e.g., SEQ ID NOs: 313, 314). In another embodiment, the T cell co-inhibitory molecule is TIM3. In some embodiments, the fusion protein is selected from: anti-IL6R-BTLA-TIM3 (e.g., SEQ ID NOs: 313, 317). In another aspect, the additional receptor ECD is SIRPa ECD. In some embodiments, the fusion protein is selected from: anti-IL6R-BTLA-SIRPa (e.g., SEQ ID NOs: 313, 316). In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL6R-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 313, 315). In another aspect, the additional receptor ECD is VEGFR ECD. In some embodiments, the fusion protein is selected from: anti-IL6R-VEGFR-BTLA (e.g., SEQ ID NOs: 324, 319).

In some embodiments, the fusion protein further comprises an additional receptor ECD. Exemplary embodiments of this fusion protein include anti-TGFb-BTLA-TIM3 (e.g., SEQ ID NOs: 393, 397); anti-TGFb-BTLA-PD1 (e.g., SEQ ID NOs: 393, 394); anti-TGFb-BTLA-SIRPa (e.g., SEQ ID NOs: 393, 396); anti-TGFb-BTLA-SIGLEC10 (e.g., SEQ ID NOs: 393, 395).

In some embodiments, the fusion protein comprises BTLA ECD and IL-15. In some embodiments, the fusion protein is IL15-Fc-BTLA (e.g., SEQ ID NO: 574) or BTLA-Fc-IL15 (e.g., SEQ ID NO: 573). In other embodiments, the fusion protein is IL12-Fc-BTLA (e.g., SEQ ID NO: 572) or BTLA-Fc-IL12 (e.g., SEQ ID NO: 571). In other embodiments, the fusion protein comprises an antibody with BTLA ECD fused to heavy chain and IL-15 fused to light chain. In other embodiments, the fusion protein comprises an antibody with BTLA ECD fused to heavy chain and IL-12 fused to light chain.

In various embodiments, the fusion proteins of the invention counteract CD47/SIRPa in the tumor microenvironment. In some embodiments, the fusion proteins comprise a ligand-binding sequence of an extracellular domain of SIRPa (e.g., SIRPa ECD).

In one embodiment, the fusion protein of the invention is an ALT that comprises an antibody that binds CD47 or CD47 ligand (e.g. SIRPa). In one example, the ALT comprises an antibody that binds CD47 and interferes with its interaction with SIRPa. In one example, the ALT comprises an antibody that binds SIRPa and interferes with its interaction with CD47. In one aspect, the antibody is an antagonist that inhibits SIRPa intracellular ITIM or ITSM signaling, thereby promoting immune cell activation. In various examples, the antibody that binds CD47 or SIRPa is fused to one or more ligand traps. In one example the CD47 or SIRPa antibody is fused to a ligand-binding sequence of the extracellular domain of PD1 (PD1 ECD). In one example the CD47 or SIRPa antibody is fused to a ligand-binding sequence of the extracellular domain of TGFbR (TGFbRII ECD). In one example the CD47 or SIRPa antibody is fused to a ligand-binding sequence of the extracellular domain of TIM3 (TIM3 ECD). In one example the CD47 or SIRPa antibody is fused to a ligand-binding sequence of the extracellular domain of BTLA (BTLA ECD). In one example the CD47 or SIRPa antibody is fused to a ligand-binding sequence of the extracellular domain of SIGLEC10 (SIGLEC10 ECD). In one example the CD47 or SIRPa antibody is fused to a ligand-binding sequence of the extracellular domain of VEGFR (VEGFR ECD). In one embodiment, the CD47 or SIRPa binding antibody is fused to multiple ligand traps selected from the following: PD1 ECD, TGFbRII ECD, TIM3 ECD, BTLA ECD, VEGFR ECD, SIGLEC10 ECD. In one aspect, a ligand trap (LT1) is fused to the heavy chain, and a second ligand trap (LT2) is fused to the light chain. In another aspect, LT1 or LT2 functions to localize the fusion protein to the tumor microenvironment. In one

In various examples, the ALT comprises a CD47 or SIRPa binding antibody, wherein the heavy chain is fused to TGFbRII ECD and the light chain is fused to PD1 ECD, BTLA ECD, TIM3 ECD, or SIGLEC10 ECD. In various examples, the ALT comprises a CD47 or SIRPa binding antibody, wherein the heavy chain is fused to VEGFR ECD and the light chain is fused to PD1 ECD, BTLA ECD, TIM3 ECD, or SIGLEC10 ECD. In various examples, the ALT comprises a CD47 or SIRPa binding antibody, wherein the heavy chain is fused to PD1 ECD and the light chain is fused to BTLA ECD, TIM3 ECD, or SIGLEC10 ECD. In various examples, the ALT comprises a CD47 or SIRPa binding antibody, wherein the heavy chain is fused to BTLA ECD and the light chain is fused to PD1 ECD, TIM3 ECD, or SIGLEC10 ECD. In various examples, the ALT comprises a CD47 or SIRPa binding antibody, wherein the heavy chain is fused to TIM3 ECD and the light chain is fused to BTLA ECD, PD1 ECD, or SIGLEC10 ECD. In various examples, the ALT comprises a CD47 or SIRPa binding antibody, wherein the heavy chain is fused to SIGLEC10 ECD and the light chain is fused to BTLA ECD, TIM3 ECD, or PD1 ECD.

In one embodiment, the fusion proteins of the invention may comprise a ligand-binding sequence of an extracellular domain of SIRPa to interrupt the interaction of SIRPa and CD47. In one embodiment, the fusion protein comprises a targeting polypeptide and the SIRPa ECD is fused to the targeting polypeptide. In some embodiments, the targeting polypeptide is an antibody and SIRPa ECD is fused to the heavy chain of the antibody. In other embodiments, the targeting polypeptide is an antibody and SIRPa ECD is fused to the light chain of the antibody.

In some embodiments, the fusion protein of the invention comprises a targeting polypeptide that is an antibody. In one embodiment, the antibody is fused to SIRPa ECD and additional ligand traps selected from the following: PD1 ECD, TGFbRII ECD, BTLA ECD, TIM3 ECD, VEGFR ECD, SIGLEC10 ECD. In one aspect, a ligand trap (LT1) is fused to the heavy chain, and a second ligand trap (LT2) is fused to the light chain. In one aspect, the SIRPa ECD is fused to the heavy chain and another ligand trap is fused to the light chain. In one aspect, the SIRPa ECD is fused to the light chain and another ligand trap is fused to the heavy chain. In various examples, the ALT comprises an antibody, wherein the heavy chain is fused to TIM3 ECD and the light chain is fused to one of PD1 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD. In various examples, the ALT comprises an antibody wherein the light chain is fused to TIM3 ECD and the heavy chain is fused to one of PD1 ECD, TGFbRII ECD, BTLA ECD, TIM3 ECD, VEGFR ECD, SIGLEC10 ECD.

In some embodiments, the fusion protein comprises SIRPa ECD and a polypeptide that inhibits the interaction of TIGIT or PVRIG with PVRL2 or PVR. In some embodiments, this fusion protein comprises an antibody that binds TIGIT or PVRIG fused to SIRPa ECD. Exemplary embodiments of this fusion protein include anti-TIGIT-SIRPa (e.g., SEQ ID NOs: 477, 139) and anti-PVRIG-SIRPa.

In some embodiments, the fusion protein comprises SIRPa ECD and a polypeptide that inhibits the interaction of VISTA and VSIG8. In some embodiments, this fusion protein comprises an antibody that binds VISTA or VSIG8 fused to SIRPa ECD. Exemplary embodiments of this fusion protein include anti-VISTA-SIRPa and anti-VSIG8-SIRPa.

In some embodiments, the fusion protein comprises SIRPa ECD and a polypeptide that inhibits the interaction of PD-1 and PD-L1. In some embodiments, this fusion protein comprises an antibody that binds PD-1 or PD-L1 fused to SIRPa ECD. Exemplary embodiments of this fusion protein include anti-PD1-SIRPa (e.g., SEQ ID NOs: 455, 101) and anti-PDL1-SIRPa (e.g., SEQ ID NOs: 465, 109).

In some embodiments, the fusion protein comprises SIRPa ECD and a polypeptide that inhibits CTLA-4. In some embodiments, this fusion protein comprises an antibody that binds CTLA-4 fused to SIRPa ECD. Exemplary embodiments of this fusion protein include anti-CTLA4-SIRPa (e.g., SEQ ID NOs: 443, 28).

In some embodiments, the fusion protein comprises SIRPa ECD and a polypeptide that inhibits TIM-3. In some embodiments, this fusion protein comprises an antibody that binds TIM-3 fused to SIRPa ECD. Exemplary embodiments of this fusion protein include anti-TIM3-SIRPa (e.g., SEQ ID NOs: 489, 141).

In some embodiments, the fusion protein comprises SIRPa ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and an additional receptor ECD. In one aspect, the SIRPa ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the SIRPa ECD is fused to the light chain and the additional receptor ECD is fused to the heavy chain

In other embodiments, the fusion protein comprises SIRPa ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and SIGLEC10 ECD. Exemplary embodiments of this fusion protein include anti-TIGIT-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 477, 471); anti-PD1-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 455, 449); anti-PDL1-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 465, 460); anti-TIM3-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 489, 483); anti-CTLA4-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 443, 437).

In a further aspect, the fusion protein comprises an antibody that binds a T cell-costimulatory molecule, SIRPa ECD, and an additional receptor ECD. In one aspect, the SIRPa ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the SIRPa ECD is fused to the light chain of the antibody and the additional receptor ECD is fused to the heavy chain of the antibody. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-41BB—SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 501, 495); anti-ICOS-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 525, 519); anti-OX40-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 513, 507).

In some embodiments, the fusion protein comprises an antibody, SIRPa ECD, and the ECD of a T cell co-stimulatory molecule. In one aspect, the SIRPa ECD is fused to heavy chain and the ECD of a T cell co-stimulatory molecule fused to light chain. Alternatively, the SIRPa ECD is fused to the light chain and the T cell co-stimulatory molecule ECD is fused to the heavy chain. In some embodiments, the fusion protein comprises SIRPa ECD and one of the following: OX40L, 41BBL, ICOSL.

In one embodiment, the fusion protein comprises SIRPa ECD and a polypeptide that binds an ectonucleotidase. In a preferred embodiment, the ectonucleotidase is either CD39 or CD73. In some embodiments, the fusion protein is an antibody that binds CD39 or CD73 fused to SIRPa ECD; for example: anti-CD39-SIRPa (e.g., SEQ ID NOs: 431, 18) or anti-CD73-SIRPa (e.g., SEQ ID NOs: 424, 24).

In some embodiments, the fusion protein comprises SIRPa ECD, an antibody that binds CD39 or CD73, and an additional receptor ECD. In some embodiments, the SIRPa ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the SIRPa ECD is fused to the light chain of the antibody and the additional receptor ECD is fused to the heavy chain of the antibody.

In some embodiments, the fusion protein comprises a tumor-targeted antibody and SIRPa ECD. In some embodiments, this tumor targeted-antibody binds a tumor growth factor or growth factor receptor. In other embodiments, this tumor targeted antibody binds a tumor cell surface molecule. In some embodiments, this fusion protein is selected from the following: anti-EGFR-SIRPa (e.g., SEQ ID NOs: 228, 43), anti-HER2-SIRPa (e.g., SEQ ID NOs: 252, 55), anti-EGFRvIII-SIRPa (e.g., SEQ ID NOs: 240, 47), anti-uPAR-SIRPa (e.g., SEQ ID NOs: 271, 162), anti-PSMA-SIRPa (e.g., SEQ ID NOs: 278, 121), anti-nectin-4-SIRPa.

In a further embodiment, the fusion protein comprises a tumor-targeted antibody, SIRPa ECD, and an additional receptor ECD. In one embodiment, the SIRPa ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the SIRPa ECD is fused to the light chain and the additional receptor ECD is fused to the heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In another embodiment, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-HER2-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 252, 246); anti-nectin4-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 264, 258); anti-EGFR—SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 228, 222); anti-EGFRvIII—SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 240, 234).

In some embodiments, the fusion protein comprises SIRPa ECD and a polypeptide that inhibits VEGF/VEGFR signaling.

In some embodiments, the fusion protein comprises SIRPa ECD and anti-VEGFR mAb with SIRPa ECD fused to either the heavy chain or light chain of the antibody. In some embodiments, this fusion protein is anti-VEGFR-SIRPa (e.g., SEQ ID NOs: 380, 148). In a further embodiment, the fusion protein may additionally comprise a receptor ECD fused to the other chain of the antibody. In some embodiments, the fusion protein is selected from anti-VEGFR-SIRPa-PD1 (e.g., SEQ ID NOs: 380, 373); anti-VEGFR-SIRPa-TIM3 (e.g., SEQ ID NOs: 380, 376); anti-VEGFR-SIRPa-BTLA (e.g., SEQ ID NOs: 380, 378); anti-VEGFR-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 380, 374).

In some embodiments, the fusion protein comprises SIRPa ECD and anti-VEGF mAb with SIRPa ECD fused to either the heavy chain or light chain of the antibody. In some embodiments, this fusion protein is anti-VEGF-SIRPa (e.g., SEQ ID NOs: 369, 32). In a further embodiment, the fusion protein may additionally comprise a receptor ECD fused to the other chain of the antibody. In some embodiments, the fusion protein is selected from anti-VEGF-SIRPa-BTLA (e.g., SEQ ID NOs: 369, 367); anti-VEGF-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 369, 363); anti-VEGF-SIRPa-TIM3 (e.g., SEQ ID NOs: 369, 365); anti-VEGF-SIRPa-PD1 (e.g., SEQ ID NOs: 369, 362)

In some embodiments, the fusion protein comprises an antibody that binds IL-17 or IL-17R and SIRPa ECD. In some embodiments, this fusion protein is selected from the following: anti-IL17-SIRPa, anti-IL17R-SIRPa (e.g., SEQ ID NOs: 333, 63).

In a further embodiment, the fusion protein comprises an antibody that binds IL-17 or IL-17R, SIRPa ECD, and an additional receptor ECD. In one embodiment, SIRPa ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, SIRPa ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL17R-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 333, 327).

In some embodiments, the fusion protein comprises an antibody that binds IL-23 or IL-23R and SIRPa ECD. If the antibody binds IL-23, it is preferred that the antibody bind the p19 subunit of IL-23 that is not shared with IL-12. In some embodiments, this fusion protein is selected from the following: anti-IL23-SIRPa (e.g., SEQ ID NOs: 345, 75), anti-IL23R-SIRPa.

In a further embodiment, the fusion protein comprises an antibody that binds IL-23 or IL-23R, SIRPa ECD, and an additional receptor ECD. In one embodiment, SIRPa ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, SIRPa ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL23-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 345, 339).

In some embodiments, the fusion protein comprises an antibody that binds IL-6 or IL-6R and SIRPa ECD. In some embodiments, this fusion protein is selected from the following: anti-IL6-SIRPa, anti-IL6R-SIRPa (e.g., SEQ ID NOs: 321, 79).

In some embodiments, the fusion protein comprises an antibody that binds IL-6 or IL-6R, SIRPa ECD, and an additional receptor ECD. In one embodiment, SIRPa ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, SIRPa ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule. In another aspect, the additional receptor ECD is SIGLEC10 ECD. In some embodiments, the fusion protein is selected from: anti-IL6R-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 321, 315).

In some embodiments, the fusion protein further comprises an additional receptor ECD. Exemplary embodiments of this fusion protein include anti-TGFb-SIRPa-BTLA (e.g., SEQ ID NOs: 401, 399); anti-TGFb-SIRPa-TIM3 (e.g., SEQ ID NOs: 401, 397); anti-TGFb-SIRPa-PD1 (e.g., SEQ ID NOs: 401, 394); anti-TGFb-SIRPa-SIGLEC10 (e.g., SEQ ID NOs: 401, 395).

In some embodiments, the fusion protein comprises SIRPa ECD and IL-15. In some embodiments, the fusion protein is IL15-Fc-SIRPa (e.g., SEQ ID NO: 586) or SIRPa-Fc-IL15 (e.g., SEQ ID NO: 585). In other embodiments, the fusion protein is IL12-Fc-SIRPa (e.g., SEQ ID NO: 584) or SIRPa-Fc-IL12 (e.g., SEQ ID NO: 583). In other embodiments, the fusion protein comprises an antibody with SIRPa ECD fused to heavy chain and IL-15 fused to light chain. In other embodiments, the fusion protein comprises an antibody with SIRPa ECD fused to heavy chain and IL-12 fused to light chain.

In various embodiments, the fusion proteins of the invention counteract SIGLEC10/CD24 in the tumor microenvironment. In some embodiments, the fusion proteins comprise a ligand-binding sequence of an extracellular domain of SIGLEC10 (e.g., SIGLEC10 ECD).

In one embodiment, the fusion protein of the invention is an ALT that comprises an antibody that binds SIGLEC10 or CD24. In one example, the ALT comprises an antibody that binds CD24 and interferes with its interaction with SIGLEC10. In one example, the ALT comprises an antibody that binds SIGLEC10 and interferes with its interaction with CD24. In one aspect, the antibody is an antagonist that inhibits SIGLEC10 intracellular ITIM or ITSM signaling, thereby promoting immune cell activation. In various examples, the antibody that binds CD24 or SIGLEC10 is fused to one or more ligand traps. In one example the CD24 or SIGLEC10 antibody is fused to a ligand-binding sequence of the extracellular domain of PD1 (PD1 ECD). In one example the CD24 or SIGLEC10 antibody is fused to a ligand-binding sequence of the extracellular domain of TGFbR (TGFbRII ECD). In one example the CD24 or SIGLEC10 antibody is fused to a ligand-binding sequence of the extracellular domain of TIM3 (TIM3 ECD). In one example the CD24 or SIGLEC10 antibody is fused to a ligand-binding sequence of the extracellular domain of BTLA (BTLA ECD). In one example the CD24 or SIGLEC10 antibody is fused to a ligand-binding sequence of the extracellular domain of SIRPa (SIRPa ECD). In one example the CD24 or SIGLEC10 antibody is fused to a ligand-binding sequence of the extracellular domain of VEGFR (VEGFR ECD). In one embodiment, the CD24 or SIGLEC10 binding antibody is fused to multiple ligand traps selected from the following: PD1 ECD, TGFbRII ECD, TIM3 ECD, BTLA ECD, VEGFR ECD, SIRPa ECD. In one aspect, a ligand trap (LT1) is fused to the heavy chain, and a second ligand trap (LT2) is fused to the light chain.

In various examples, the ALT comprises a CD24 or SIGLEC10 binding antibody, wherein the heavy chain is fused to TGFbRII ECD and the light chain is fused to PD1 ECD, BTLA ECD, TIM3 ECD, or SIRPa ECD. In various examples, the ALT comprises a CD24 or SIGLEC10 binding antibody, wherein the heavy chain is fused to VEGFR ECD and the light chain is fused to PD1 ECD, BTLA ECD, TIM3 ECD, or SIRPa ECD. In various examples, the ALT comprises a CD24 or SIGLEC10 binding antibody, wherein the heavy chain is fused to PD1 ECD and the light chain is fused to BTLA ECD, TIM3 ECD, or SIRPa ECD. In various examples, the ALT comprises a CD24 or SIGLEC10 binding antibody, wherein the heavy chain is fused to BTLA ECD and the light chain is fused to PD1 ECD, TIM3 ECD, or SIRPa ECD. In various examples, the ALT comprises a CD24 or SIGLEC10 binding antibody, wherein the heavy chain is fused to TIM3 ECD and the light chain is fused to BTLA ECD, PD1 ECD, or SIRPa ECD. In various examples, the ALT comprises a CD24 or SIGLEC10 binding antibody, wherein the heavy chain is fused to SIRPa ECD and the light chain is fused to BTLA ECD, TIM3 ECD, or PD1 ECD.

In one embodiment, the fusion proteins of the invention may comprise a ligand-binding sequence of an extracellular domain of SIGLEC10 to interrupt the interaction of SIGLEC10 and CD24. In one embodiment, the fusion protein comprises a targeting polypeptide and the SIGLEC10 ECD is fused to the targeting polypeptide. In some embodiments, the targeting polypeptide is an antibody and SIGLEC10 ECD is fused to the heavy chain of the antibody. In other embodiments, the targeting polypeptide is an antibody and SIGLEC10 ECD is fused to the light chain of the antibody.

In some embodiments, the fusion protein of the invention comprises a targeting polypeptide that is an antibody. In one embodiment, the antibody is fused to SIGLEC10 ECD and additional ligand traps selected from the following: PD1 ECD, TGFbRII ECD, BTLA ECD, TIM3 ECD, VEGFR ECD, SIRPa ECD. In one aspect, a ligand trap (LT1) is fused to the heavy chain, and a second ligand trap (LT2) is fused to the light chain. In one aspect, the SIGLEC10 ECD is fused to the heavy chain and another ligand trap is fused to the light chain. In one aspect, the SIGLEC10 ECD is fused to the light chain and another ligand trap is fused to the heavy chain. In various examples, the ALT comprises an antibody, wherein the heavy chain is fused to TIM3 ECD and the light chain is fused to one of PD1 ECD, BTLA ECD, SIGLEC10 ECD, or SIRPa ECD. In various examples, the ALT comprises an antibody wherein the light chain is fused to TIM3 ECD and the heavy chain is fused to one of PD1 ECD, TGFbRII ECD, BTLA ECD, TIM3 ECD, VEGFR ECD, SIRPa ECD.

In some embodiments, the fusion protein comprises SIGLEC10 ECD and a polypeptide that inhibits the interaction between CD47 and SIRPa. In one embodiment, this fusion protein comprises SIGLEC10 ECD and a polypeptide that binds CD47. In one embodiment, this fusion protein is anti-CD47 mAb fused to SIGLEC10 ECD (anti-CD47-SIGLEC10 (e.g., SEQ ID NOs: 389, 22)). In another embodiment, this fusion protein comprises SIRPa ECD and SIGLEC10 ECD. In one embodiment, this fusion protein is SIRPa-Fc-SIGLEC10 (e.g., SEQ ID NO: 549) or SIGLEC10-Fc-SIRPa (e.g., SEQ ID NO: 543).

In a further aspect, the fusion protein comprises SIGLEC10 ECD, a polypeptide that inhibits the interaction between CD47 and SIRPa, and another polypeptide that inhibits a T cell co-inhibitory molecule. In some embodiments, this fusion protein comprises anti-CD47 mAb with SIGLEC10 ECD fused to the heavy chain or light chain; and a T cell co-inhibitory molecule ECD fused to the other chain. In a particular embodiment, this fusion protein is anti-CD47-SIGLEC10-PD1 (e.g., SEQ ID NOs: 389, 384). In another embodiment, this fusion protein is anti-CD47-SIGLEC10-TIM3 (e.g., SEQ ID NOs: 389, 386).

In another aspect, the fusion protein comprises SIGLEC10 ECD, SIRPa ECD, and an antibody with a heavy chain and light chain. In one aspect, the SIGLEC10 ECD is fused to the heavy chain of the antibody and the SIRPa ECD is fused to the light chain of the antibody. In another aspect, the SIGLEC10 ECD is fused to the light chain of the antibody and the SIRPa ECD is fused to the heavy chain of the antibody. In some embodiments, the antibody of said fusion protein binds a T cell co-inhibitory molecule as an antagonist. Exemplary embodiments of such fusion proteins include anti-CTLA4-SIGLEC10-SIRPa (e.g., SEQ ID NOs: 442, 438), anti-PD1-SIGLEC10-SIRPa (e.g., SEQ ID NOs: 454, 450), and anti-PDL1-SIGLEC10-SIRPa (e.g., SEQ ID NOs: 463, 461). In other embodiments, the antibody of said fusion protein binds a T cell co-stimulatory molecule as an agonist. Exemplary embodiments of this fusion protein include anti-OX40-SIGLEC10-SIRPa (e.g., SEQ ID NOs: 512, 508), anti-41BB-SIGLEC10-SIRPa (e.g., SEQ ID NOs: 500, 496), and anti-CD40-SIGLEC10-SIRPa. In other embodiments, the antibody of said fusion protein is a tumor-targeted antibody. In some embodiments, this tumor targeted-antibody binds a tumor growth factor or growth factor receptor. In other embodiments, this tumor targeted antibody binds a tumor cell surface molecule. Exemplary embodiments of this fusion protein include anti-EGFR-SIGLEC10-SIRPa (e.g., SEQ ID NOs: 227, 223), anti-HER2-SIGLEC10-SIRPa (e.g., SEQ ID NOs: 251, 247), anti-EGFRvIII-SIGLEC10-SIRPa (e.g., SEQ ID NOs: 239, 235), anti-uPAR-SIGLEC10-SIRPa, and anti-PSMA-SIGLEC10-SIRPa.

In other embodiments, the antibody of said fusion protein binds a member of the TGFb pathway. In some embodiments, this antibody binds TGFb, TGFbR, or GARP. Exemplary embodiments of this fusion protein include anti-TGFb-SIGLEC10-SIRPa (e.g., SEQ ID NOs: 400, 396), anti-TGFbR-SIGLEC10-SIRPa, and anti-GARP-SIGLEC10-SIRPa.

In other embodiments, the antibody of said fusion protein binds VEGF or VEGFR. Exemplary embodiments of this fusion protein include anti-VEGF-SIGLEC10-SIRPa (e.g., SEQ ID NOs: 368, 364) and anti-VEGFR-SIGLEC10-SIRPa (e.g., SEQ ID NOs: 379, 375).

In some embodiments, the fusion protein comprises SIGLEC10 ECD and a polypeptide that inhibits the interaction of TIGIT or PVRIG with PVRL2 or PVR. In some embodiments, this fusion protein comprises an antibody that binds TIGIT or PVRIG fused to SIGLEC10 ECD. Exemplary embodiments of this fusion protein include anti-TIGIT-SIGLEC10 (e.g., SEQ ID NOs: 476, 139) and anti-PVRIG-SIGLEC10.

In some embodiments, the fusion protein comprises SIGLEC10 ECD and a polypeptide that inhibits the interaction of VISTA and VSIG8. In some embodiments, this fusion protein comprises an antibody that binds VISTA or VSIG8 fused to SIGLEC10 ECD. Exemplary embodiments of this fusion protein include anti-VISTA-SIGLEC10 and anti-VSIG8-SIGLEC10.

In some embodiments, the fusion protein comprises SIGLEC10 ECD and a polypeptide that inhibits the interaction of PD-1 and PD-L1. In some embodiments, this fusion protein comprises an antibody that binds PD-1 or PD-L1 fused to SIGLEC10 ECD. Exemplary embodiments of this fusion protein include anti-PD1-SIGLEC10 (e.g., SEQ ID NOs: 454, 101) and anti-PDL1-SIGLEC10 (e.g., SEQ ID NOs: 463, 109).

In some embodiments, the fusion protein comprises SIGLEC10 ECD and a polypeptide that inhibits CTLA-4. In some embodiments, this fusion protein comprises an antibody that binds CTLA-4 fused to SIGLEC10 ECD. Exemplary embodiments of this fusion protein include anti-CTLA4-SIGLEC10 (e.g., SEQ ID NOs: 442, 28).

In some embodiments, the fusion protein comprises SIGLEC10 ECD and a polypeptide that inhibits TIM-3. In some embodiments, this fusion protein comprises an antibody that binds TIM-3 fused to SIGLEC10 ECD. Exemplary embodiments of this fusion protein include anti-TIM3-SIGLEC10 (e.g., SEQ ID NOs: 488, 141).

In some embodiments, the fusion protein comprises SIGLEC10 ECD, an antibody that binds and disables a T cell co-inhibitory molecule, and an additional receptor ECD. In one aspect, the SIGLEC10 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the SIGLEC10 ECD is fused to the light chain and the additional receptor ECD is fused to the heavy chain.

Fusion proteins comprising SIGLEC10 ECD and antibody that binds a T cell co-stimulatory molecule as an agonist

In a further aspect, the fusion protein comprises an antibody that binds a T cell-costimulatory molecule, SIGLEC10 ECD, and an additional receptor ECD. In one aspect, the SIGLEC10 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the SIGLEC10 ECD is fused to the light chain of the antibody and the additional receptor ECD is fused to the heavy chain of the antibody. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule.

In some embodiments, the fusion protein comprises an antibody, SIGLEC10 ECD, and the ECD of a T cell co-stimulatory molecule. In one aspect, the SIGLEC10 ECD is fused to heavy chain and the ECD of a T cell co-stimulatory molecule fused to light chain. Alternatively, the SIGLEC10 ECD is fused to the light chain and the T cell co-stimulatory molecule ECD is fused to the heavy chain. In some embodiments, the fusion protein comprises SIGLEC10 ECD and one of the following: OX40L, 41BBL, ICOSL.

In one embodiment, the fusion protein comprises SIGLEC10 ECD and a polypeptide that binds an ectonucleotidase. In a preferred embodiment, the ectonucleotidase is either CD39 or CD73. In some embodiments, the fusion protein is an antibody that binds CD39 or CD73 fused to SIGLEC10 ECD; for example: anti-CD39-SIGLEC10 (e.g., SEQ ID NOs: 430, 18) or anti-CD73-SIGLEC10 (e.g., SEQ ID NOs: 423, 24).

In some embodiments, the fusion protein comprises SIGLEC10 ECD, an antibody that binds CD39 or CD73, and an additional receptor ECD. In some embodiments, the SIGLEC10 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the SIGLEC10 ECD is fused to the light chain of the antibody and the additional receptor ECD is fused to the heavy chain of the antibody.

In some embodiments, the fusion protein comprises a tumor-targeted antibody and SIGLEC10 ECD. In some embodiments, this tumor targeted-antibody binds a tumor growth factor or growth factor receptor. In other embodiments, this tumor targeted antibody binds a tumor cell surface molecule. In some embodiments, this fusion protein is selected from the following: anti-EGFR-SIGLEC10 (e.g., SEQ ID NOs: 227, 43), anti-HER2-SIGLEC10 (e.g., SEQ ID NOs: 251, 55), anti-EGFRvIII-SIGLEC10 (e.g., SEQ ID NOs: 239, 47), anti-uPAR-SIGLEC10 (e.g., SEQ ID NOs: 270, 162), anti-PSMA-SIGLEC10 (e.g., SEQ ID NOs: 277, 121), anti-nectin-4-SIGLEC10.

In a further embodiment, the fusion protein comprises a tumor-targeted antibody, SIGLEC10 ECD, and an additional receptor ECD. In one embodiment, the SIGLEC10 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, the SIGLEC10 ECD is fused to the light chain and the additional receptor ECD is fused to the heavy chain.

In some embodiments, the fusion protein comprises SIGLEC10 ECD and a polypeptide that inhibits VEGF/VEGFR signaling.

In some embodiments, the fusion protein comprises SIGLEC10 ECD and anti-VEGFR mAb with SIGLEC10 ECD fused to either the heavy chain or light chain of the antibody. In some embodiments, this fusion protein is anti-VEGFR-SIGLEC10 (e.g., SEQ ID NOs: 379, 148). In a further embodiment, the fusion protein may additionally comprise a receptor ECD fused to the other chain of the antibody.

In some embodiments, the fusion protein comprises SIGLEC10 ECD and anti-VEGF mAb with SIGLEC10 ECD fused to either the heavy chain or light chain of the antibody. In some embodiments, this fusion protein is anti-VEGF-SIGLEC10 (e.g., SEQ ID NOs: 368, 32). In a further embodiment, the fusion protein may additionally comprise a receptor ECD fused to the other chain of the antibody.

In other embodiments, the fusion protein comprises SIGLEC10 ECD and VEGFR ECD. In one embodiment, this fusion protein is SIGLEC10-Fc-VEGFR (e.g., SEQ ID NO: 546). In another embodiment, this fusion protein is VEGFR-Fc-SIGLEC10 (e.g., SEQ ID NO: 567).

In some embodiments, the fusion protein comprises an antibody that binds IL-17 or IL-17R and SIGLEC10 ECD. In some embodiments, this fusion protein is selected from the following: anti-IL17-SIGLEC10, anti-IL17R-SIGLEC10 (e.g., SEQ ID NOs: 332, 63).

In a further embodiment, the fusion protein comprises an antibody that binds IL-17 or IL-17R, SIGLEC10 ECD, and an additional receptor ECD. In one embodiment, SIGLEC10 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, SIGLEC10 ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule.

In some embodiments, the fusion protein comprises an antibody that binds IL-23 or IL-23R and SIGLEC10 ECD. If the antibody binds IL-23, it is preferred that the antibody bind the p19 subunit of IL-23 that is not shared with IL-12. In some embodiments, this fusion protein is selected from the following: anti-IL23-SIGLEC10 (e.g., SEQ ID NOs: 344, 75), anti-IL23R-SIGLEC10.

In a further embodiment, the fusion protein comprises an antibody that binds IL-23 or IL-23R, SIGLEC10 ECD, and an additional receptor ECD. In one embodiment, SIGLEC10 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, SIGLEC10 ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule.

In some embodiments, the fusion protein comprises an antibody that binds IL-6 or IL-6R and SIGLEC10 ECD. In some embodiments, this fusion protein is selected from the following: anti-IL6-SIGLEC10, anti-IL6R-SIGLEC10 (e.g., SEQ ID NOs: 320, 79).

In a further embodiment, the fusion protein comprises an antibody that binds IL-6 or IL-6R, SIGLEC10 ECD, and an additional receptor ECD. In one embodiment, SIGLEC10 ECD is fused to the heavy chain of the antibody and the additional receptor ECD is fused to the light chain of the antibody. Alternatively, SIGLEC10 ECD is fused to light chain and additional receptor ECD is fused to heavy chain. In some embodiments, the additional receptor ECD is the ECD of a T cell co-inhibitory molecule.

In some embodiments, the fusion protein comprises SIGLEC10 ECD and IL-15. In some embodiments, the fusion protein is IL15-Fc-SIGLEC10 (e.g., SEQ ID NO: 582) or SIGLEC10-Fc-IL15 (e.g., SEQ ID NO: 581). In other embodiments, the fusion protein is IL12-Fc-SIGLEC10 (e.g., SEQ ID NO: 580) or SIGLEC10-Fc-IL12 (e.g., SEQ ID NO: 579). In other embodiments, the fusion protein comprises an antibody with SIGLEC10 ECD fused to heavy chain and IL-15 fused to light chain. In other embodiments, the fusion protein comprises an antibody with SIGLEC10 ECD fused to heavy chain and IL-12 fused to light chain.

In some embodiments, this invention covers fusion proteins comprising two different extracellular domains (ECDs).

In some embodiments, ECD #1 is a ligand-binding fragment of PD1 ECD. In some embodiments, ECD #2 is a ligand-binding fragment of a T cell co-inhibitory molecule. In some embodiments, ECD #2 is BTLA ECD or TIM3 ECD. In other embodiments, ECD #2 is VEGFR ECD. In other embodiments, ECD #2 is TGFbRII ECD. In other embodiments, ECD #2 is a cytokine receptor ECD. In other embodiments, ECD #2 is the ECD of a receptor whose ligation inhibits phagocytosis. In some embodiments, ECD #2 is SIRPa ECD or SIGLEC10 ECD.

In some embodiments, ECD #1 is a ligand-binding fragment of BTLA ECD. In some embodiments, ECD #2 is a ligand-binding fragment of a T cell co-inhibitory molecule. In some embodiments, ECD #2 is TIM3 ECD. In other embodiments, ECD #2 is VEGFR ECD. In other embodiments, ECD #2 is TGFbRII ECD. In other embodiments, ECD #2 is a cytokine receptor ECD. In other embodiments, ECD #2 is the ECD of a receptor whose ligation inhibits phagocytosis. In some embodiments, ECD #2 is SIRPa ECD or SIGLEC10 ECD.

In some embodiments, ECD #1 is a ligand-binding fragment of TIM3 ECD. In some embodiments, ECD #2 is a ligand-binding fragment of a T cell co-inhibitory molecule. In other embodiments, ECD #2 is VEGFR ECD. In other embodiments, ECD #2 is TGFbRII ECD. In other embodiments, ECD #2 is a cytokine receptor ECD. In other embodiments, ECD #2 is the ECD of a receptor whose ligation inhibits phagocytosis. In some embodiments, ECD #2 is SIRPa ECD or SIGLEC10 ECD.

In some embodiments, ECD #1 is a ligand-binding fragment of TGFbRII ECD. In some embodiments, ECD #2 is a ligand-binding fragment of a T cell co-inhibitory molecule. In other embodiments, ECD #2 is VEGFR ECD. In other embodiments, ECD #2 is a cytokine receptor ECD. In other embodiments, ECD #2 is the ECD of a receptor whose ligation inhibits phagocytosis. In some embodiments, ECD #2 is SIRPa ECD or SIGLEC10 ECD. In other embodiments, ECD #2 is the ECD of a T cell co-stimulatory ligand. In some embodiments, ECD #2 is one of OX40L, 41BBL, ICOSL, GITRL, LIGHT, CD70, CD40L, CD30L.

In some embodiments, ECD #1 is a ligand-binding fragment of VEGFR ECD. In some embodiments, ECD #2 is a ligand-binding fragment of a T cell co-inhibitory molecule. In other embodiments, ECD #2 is a cytokine receptor ECD. In other embodiments, ECD #2 is the ECD of a receptor whose ligation inhibits phagocytosis. In some embodiments, ECD #2 is SIRPa ECD or SIGLEC10 ECD. In other embodiments, ECD #2 is the ECD of a T cell co-stimulatory ligand. In some embodiments, ECD #2 is one of OX40L, 41BBL, ICOSL, GITRL, LIGHT, CD70, CD40L, CD30L.

In some embodiments, ECD #1 is a ligand-binding fragment of SIRPa ECD. In some embodiments, ECD #2 is a ligand-binding fragment of a T cell co-inhibitory molecule. In other embodiments, ECD #2 is a cytokine receptor ECD. In other embodiments, ECD #2 is the ECD of a receptor whose ligation inhibits phagocytosis. In some embodiments, ECD #2 is SIGLEC 10 ECD.

In some embodiments, ECD #1 is a ligand-binding fragment of SIGLEC10 ECD. In some embodiments, ECD #2 is a ligand-binding fragment of a T cell co-inhibitory molecule.

In other embodiments, ECD #2 is a cytokine receptor ECD. In other embodiments, ECD #2 is the ECD of a receptor whose ligation inhibits phagocytosis. In other embodiments, ECD #2 is the ECD of a T cell co-stimulatory ligand. In some embodiments, ECD #2 is one of OX40L, 41BBL, ICOSL, GITRL, LIGHT, CD70, CD40L, CD30L.

In various embodiments, the invention provides preferred fusion proteins for treatment of cancer by counteracting key ligands/receptors that promote angiogenesis and immune dysfunction in the TME.

In one embodiment, the invention describes VEGF or VEGFR binding fusion proteins (ALT or ECD-ECD comprising a VEGF antibody, VEGFR antibody, or VEGFR ECD). In various embodiments, the ALT or ECD-ECD enables preferential localization of VEGF blockade to the TME.

In one embodiment, the VEGF/VEGFR blocking fusion protein of the invention comprises a tumor targeted antibody fused to VEGFR ECD. In various examples, without being limited to them, the ALT comprises an antibody that targets a tumor-associated cell surface antigen or molecule wherein the heavy chain is fused to VEGFR ECD (e.g. anti-HER2-VEGFR ECD; anti-EGFRvIII-VEGFR ECD; anti-PSMA-VEGFR ECD; anti-CEA-VEGFR ECD). In another aspect, the light chain of the ALT may be additionally fused to a receptor ECD that binds a ligand expressed on tumor cells or the TME. In various examples the additional receptor ECD fused to the light chain is PD1 ECD, TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD.

In another aspect the ALT may be any antibody wherein the heavy chain is fused to VEGFR ECD, and the light chain is fused to another receptor ECD that binds a ligand expressed on tumor cells or the TME. In various examples the additional receptor ECD fused to the light chain is PD1 ECD, TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD.

In another embodiment, the VEGF/VEGFR blocking ALT comprises a VEGF or VEGFR binding antibody fused to a receptor ECD that binds a ligand expressed on tumor cells or the TME. In various examples the ALT contains PD1 ECD (e.g. anti-VEGF-PD1 ECD to bind PDL1/2 on tumor cells), or BTLA ECD (anti-VEGF-BTLA ECD to bind HVEM on tumor cells), or TIM3 ECD (anti-VEGF-TIM3 ECD to bind CEACAM1/5 on tumor cells) or SIRPa ECD (anti-VEGF-SIRPa ECD to bind CD47 on tumor cells) or SIGLEC10 ECD (anti-VEGF-SIGLEC10 ECD). In another aspect, the VEGF-binding ECD-ECD may comprise a polypeptide containing VEGFR ECD and a receptor ECD that binds a ligand expressed on tumor cells or the TME (e.g. PD1 ECD, BTLA ECD, TIM3 ECD, SIRPa ECD, SIGLEC10 ECD).

In another embodiment, the VEGF/VEGFR binding fusion protein of the invention simultaneously binds CD47. In one aspect, the ALT comprises a CD47 binding antibody fused to VEGFR ECD. In another aspect the heavy chain is fused to VEGFR ECD, and the light chain is fused to another receptor ECD that binds a ligand expressed on tumor cells or the TME. In various examples the additional receptor ECD fused to the light chain is PD1 ECD, TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD. In another aspect, the ALT comprises a VEGF binding antibody or VEGFR binding antibody fused to SIRPa ECD. In another aspect, the ECD-ECD comprises VEGFR ECD and SIRPa ECD (e.g. VEGFR ECD-Fc-SIRPa ECD; SIRPa ECD-Fc-VEGFR ECD).

In another embodiment, the VEGF/VEGFR binding fusion protein of the invention binds VEGF or VEGFR and disrupts a ligand/receptor that promotes TH17 cell differentiation/function or angiogenesis in the TME.

In another embodiment, the VEGF/VEGFR binding fusion protein of the invention binds VEGF and TGFb. In one aspect a TGFb binding antibody is fused to VEGFR ECD. In one aspect a GARP or LAP binding antibody is fused to VEGFR ECD. In another aspect, a VEGF or VEGFR binding antibody is fused to TGFbRII ECD. In another aspect, the light chain of the ALT may be additionally fused to a receptor ECD that binds a ligand expressed on tumor cells or the TME. In various examples the additional receptor ECD fused to the light chain is PD1 ECD, TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD. In another aspect, an ECD-ECD comprises VEGFR ECD and TGFbRII ECD (VEGFR ECD-Fc-TGFbRII ECD).

In another embodiment, the VEGF/VEGFR binding fusion protein of the invention simultaneously binds and disables a-IL17R or IL17. In one aspect, the ALT comprises an IL17R antibody fused to VEGFR ECD. In another aspect, a VEGF or VEFR antibody is fused to an anti-IL17 nanobody. In another aspect, VEFR ECD is fused to an anti-IL17 nanobody. In another embodiment, the VEGF/VEGFR binding ALT simultaneously binds and disables a-IL6R or IL6. In one aspect, the ALT comprises an IL6R or IL6 binding antibody fused to VEGFR ECD. In another embodiment, the VEGF/VEGFR binding ALT simultaneously binds and disables a-IL23 or IL23R. In one aspect, the ALT comprises an IL23 or IL23R binding antibody fused to VEGFR ECD. In another embodiment, the VEGF/VEGFR binding ALT simultaneously binds and disables a-IL1 or IL1R. In one aspect, the ALT comprises an IL1 or IL1R binding antibody fused to VEGFR ECD. In an additional aspect, the ALT may be any antibody (targeting IL17, IL17R, IL23, IL23R, IL1, IL1R, IL6, or IL6R) wherein the heavy chain is fused to VEGFR ECD, and the light chain is fused to another receptor ECD (e.g. SIRPa ECD; BTLA ECD, TIM3 ECD, or PD1 ECD).

In another preferred embodiment the VEGF/VEGFR binding fusion protein of the invention binds VEGF and a co-inhibitory molecule. In one aspect a the ALT comprises an antibody that binds a T cell co-inhibitory molecule (e.g. CTLA-4, PD-L1, TIM3, BTLA, HVEM, TIGIT, PVRIG, PVRL2, PVR, VISTA, VSIG8) is fused to VEGFR ECD (e.g. a-CTLA4-VEGFR, a-PDL1-VEGFR, a-PD1-VEGFR, a-TIM3-VEGFR, a-BTLA mAb-VEGFR, a-HVEM mAb-VEGFR). In an additional aspect, the ALT may comprise the antibody wherein the heavy chain is fused to VEGFR ECD, and the light chain is fused to another receptor ECD (e.g. SIRPacd; BTLA ECD, TIM3 ECD, or PD1 ECD). In another aspect the ECD-ECD comprises VEGFR ECD and another receptor that binds a ligand expressed on tumor cells (e.g. PDL1/2, HVEM, CEACAM1/5, SIRPa). Examples of such ECD-ECDs include (VEGFR ECD-Fc-BTLA ECD, VEGFR ECD-Fc-PD1 ECD, VEGFR ECD-Fc-TIM3 ECD, VEGFR ECD-Fc-SIRPa ECD, VEGFR ECD-Fc-SIGLEC10 ECD).

In another embodiment, the VEGF/VEGFR binding fusion protein of the invention binds VEGF and a T cell co-stimulatory molecule. In one aspect a the ALT comprises an antibody that binds a T cell co-stumulatory molecule (e.g. 41BB, OX40, CD40, ICOS, GITR, DNAM) is fused to VEGFR ECD (e.g. a-41BB-VEGFR ECD, a-OX40-VEGFR ECD, a-CD40-VEGFR ECD, a-ICOS-VEGFR ECD, a-GITR-VEGFR ECD, a-DNAM-VEGFR ECD). In another aspect, the ALT may be any antibody wherein the heavy chain is fused to VEGFR ECD, and the light chain is fused to another receptor ECD (e.g. SIRPa ECD; BTLA ECD, TIM3 ECD, or PD1 ECD, SIGLEC10 ECD). In another aspect the ECD-ECD comprises VEGFR ECD and another co-stimulatory ligand (e.g. 41BBL, OX40L, GITRL, CD40L, ICOSL). Examples of such ECD-ECDs include (VEGFR ECD-Fc-41BBL, VEGFR ECD-Fc-OX40L, VEGFR ECD-Fc-ICOSL).

In another embodiment, the VEGF/VEGFR binding fusion protein of the invention comprises an antibody that binds either CD73 or CD39, fused to VEGFR ECD (a-CD73-VEGFR ECD and a-CD39-VEGFR ECD). In another aspect, the ALT may be any antibody wherein the heavy chain is fused to VEGFR ECD, and the light chain is fused to another receptor ECD that binds a ligand expressed on tumor cells or the TME (e.g. SIRPa ECD; BTLA ECD, TIM3 ECD, or PD1 ECD, SIGLEC10 ECD).

In another aspect, the ALT may be any antibody wherein the heavy chain is fused to VEGFR ECD, and the light chain is fused to another receptor ECD that binds a ligand expressed on tumor cells or the TME (e.g. SIRPa ECD; BTLA ECD, TIM3 ECD, or PD1 ECD, SIGLEC10 ECD).

In one embodiment, the invention describes TGFb or TGFbR blocking fusion proteins. In various aspects, the fusion proteins are an ALT or ECD-ECD comprising an antibody that binds TGFb, TGFbR, GARP, or LAP, or comprising TGFbRII ECD. In various embodiments, the ALT or ECD-ECD enables preferential localization of TGFb blockade to the TME.

In one aspect, the TGFb/TGFBR blocking ALT comprises a tumor targeted antibody fused to TGFbRII ECD. In various examples, without being limited to them, the ALT comprises an antibody that targets a tumor-associated cell surface antigen or molecule fused to TGFbRII ECD (e.g. anti-HER2-TGFbRII ECD; anti-EGFR-TGFbRII ECD; anti-EGFRvIII-TGFbRII ECD; anti-PSMA-TGFbRII ECD; anti-CEA-TGFbRII ECD). In another aspect, the light chain of the ALT may be additionally fused to a receptor ECD that binds a ligand expressed on tumor cells or the TME. In various examples the additional receptor ECD fused to the light chain is PD1 ECD, TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD.

In another aspect the ALT may be any antibody wherein the heavy chain is fused to TGFbRII ECD, and the light chain is fused to another receptor ECD that binds a ligand expressed on tumor cells or the TME. In various examples the additional receptor ECD fused to the light chain is PD1 ECD, TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD.

In another aspect, the TGFb/TGFBR blocking ALT comprises a TGFb or TGFBR or GARP or LAP binding antibody fused to a receptor ECD that binds a ligand expressed on tumor cells or the TME. In various examples the ALT contains PD1 ECD to bind PDL1/2 on tumor cells (e.g. anti-TGFb-PD1 ECD; anti-LAP-PD1 ECD; anti-GARP-PD1 ECD), or BTLA ECD to bind HVEM on tumor cells (anti-TGFb-BTLA ECD; anti-LAP-BTLA ECD; anti-GARP-BTLA ECD), or TIM3 ECD to bind CEACAM1/5 on tumor cells (anti-TGFb-TIM3 ECD; anti-LAP-TIM3 ECD; anti-GARP-TIM3 ECD), or SIRPa ECD to bind CD47 on tumor cells (anti-TGFb-SIRP ECD; anti-LAP-SIRPa ECD; anti-GARP-SIRPa ECD)) or SIGLEC10 ECD. In another aspect, the ALT may be TGFb or TGFBR or GARP or LAP binding antibody wherein the heavy chain is fused to one receptor ECD, and the light chain is fused to another receptor ECD that binds a ligand expressed on tumor cells or the TME (e.g. SIRPa ECD; BTLA ECD, TIM3 ECD, or PD1 ECD, or SIGLEC10 ECD). In another embodiment, the TGFb-binding ECD-ECD may comprise a polypeptide containing TGFbRII ECD and a receptor ECD that binds a ligand expressed on tumor cells or the TME (e.g. PD1 ECD, BTLA ECD, TIM3 ECD, SIRPa ECD, SIGLEC10 ECD).

In another preferred embodiment the TGFb/TGFBR blocking ALT or ECD-ECD simultaneously binds CD47. In one aspect, the ALT comprises a CD47 binding antibody fused to TGFbRII ECD. In another aspect the heavy chain is fused to TGFbRII ECD, and the light chain is fused to another receptor ECD that binds a ligand expressed on tumor cells or the TME. In various examples the additional receptor ECD fused to the light chain is PD1 ECD, TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD. In another aspect, the ALT comprises a TGFb or TGFbR or LAP or GARP binding antibody fused to SIRPa ECD. In another aspect, the heavy chain is fused to SIRPa ECD, and the light chain is fused to another receptor ECD that binds a ligand expressed on tumor cells or the TME (e.g. BTLA ECD, TIM3 ECD, or PD1 ECD, or SIGLEC10 ECD). In another aspect, the ECD-ECD comprises TGFbRII ECD and SIRPa ECD (e.g. TGFbRII ECD-Fc-SIRPa ECD; SIRPa ECD-Fc-TGFbRII ECD).

In a preferred embodiment, the TGFb/TGFBR blocking ALT or ECD-ECD binds TGFb or TGFbR or LAP or GARP, and disrupts a ligand/receptor that promotes TH17 cell differentiation/function and angiogenesis in the TME.

In another embodiment, the TGFb/TGFBR blocking fusion protein of the invention binds VEGF and either TGFb, TGFbR, LAP or GARP. In one aspect a TGFb or TGFBR or GARP or LAP binding antibody is fused to VEGFR ECD. In another aspect, the ALT may be a TGFb or TGFBR or GARP or LAP binding antibody wherein the heavy chain is fused to VEGFR ECD, and the light chain is fused to another receptor ECD that binds a ligand expressed on tumor cells or the TME (e.g. SIRPa ECD; BTLA ECD, TIM3 ECD, or PD1 ECD or SIGLEC10 ECD). In another aspect, a VEGF or VEGFR binding antibody is fused to TGFbRII ECD. In another aspect, the ALT may be a VEGF or VEGFR antibody wherein the heavy chain is fused to TGFbRII ECD, and the light chain is fused to another receptor ECD that binds a ligand expressed on tumor cells or the TME (e.g. SIRPa ECD; BTLA ECD, TIM3 ECD, or PD1 ECD or SIGLEC10 ECD). In another aspect, an ECD-ECD comprises VEGFR ECD and TGFbRII ECD (VEGFR ECD-Fc-TGFbRII ECD).

In another embodiment, the TGFb/TGFBR blocking ALT simultaneously binds and disables a-IL17R or IL17. In one aspect, the ALT comprises an IL17R antibody fused to TGFbRII ECD. In another aspect, a TGFb or TGFBR or GARP or LAP binding antibody is fused to an anti-IL17 nanobody. In another aspect, TGFbRII ECD is fused to an anti-IL17 nanobody. In another embodiment, the TGFb/TGFBR blocking ALT simultaneously binds and disables a-IL6R or IL6. In one aspect, the ALT comprises an IL6R or IL6 binding antibody fused to TGFbRII ECD. In another embodiment, the TGFb/TGFBR blocking ALT simultaneously binds and disables a-IL23 or IL23R. In one aspect, the ALT comprises an IL23 or IL23R binding antibody fused to TGFbRII ECD. In another embodiment, the TGFb/TGFBR blocking ALT simultaneously binds and disables a-IL1 or IL1R. In one aspect, the ALT comprises an IL1 or IL1R binding antibody fused to TGFbRII ECD. In another aspect, the light chain of the ALT comprising an antibody (that targets IL17R, IL17, IL23R, IL23, IL6R, IL6, IL1R, or IL1) may be additionally fused to a receptor ECD that binds a ligand expressed on tumor cells or the TME. In various examples the additional receptor ECD fused to the light chain is PD1 ECD, TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD.

In another preferred embodiment the TGFb/TGFBR binding ALT or ECD-ECD binds either TGFb or TGFbR or GARP or LAP, and a co-inhibitory molecule. In one aspect a the ALT comprises an antibody that binds a T cell co-inhibitory molecule (e.g. CTLA-4, PD-L1, TIM3, BTLA, HVEM, TIGIT, PVRIG, PVRL2, PVR, VISTA, VSIG8) is fused to TGFbRII ECD (e.g. a-CTLA4-TGFbRII, a-PDL1-TGFbRII, a-PD1-TGFbRII, a-TIM3-TGFbRII, a-BTLA mAb-TGFbRII, a-HVEM-TGFbRII). In an additional aspect, the ALT may comprise the antibody wherein the heavy chain is fused to TGFbRII ECD, and the light chain is fused to another receptor ECD that binds a ligand expressed on tumor cells or the TME (e.g. SIRPa ECD; BTLA ECD, TIM3 ECD, or PD1 ECD or SIGLEC10 ECD). In another aspect the ECD-ECD comprises TGFbRII ECD and another receptor ECD that binds a ligand expressed on tumor cells (e.g. PDL1/2, HVEM, CEACAM1/5, SIRPa). Examples of such ECD-ECDs include (TGFbRII ECD-Fc-BTLA ECD, TGFbRII ECD-Fc-PD1 ECD, TGFbRII ECD-Fc-TIM3 ECD, TGFbRII ECD-Fc-SIRPa ECD, TGFbRII ECD-Fc-SIGLEC10 ECD).

In another embodiment, the TGFb/TGFBR binding ALT or ECD-ECD binds TGFb and a T cell co-stimulatory molecule. In one aspect a the ALT comprises an antibody that binds a T cell co-stimulatory molecule (e.g. 41BB, OX40, CD40, ICOS, GITR, DNAM) is fused to TGFbRII ECD (e.g. a-41BB-TGFbRII ECD, a-OX40-TGFbRII ECD, a-CD40-TGFbRII ECD, a-ICOS-TGFbRII ECD, a-GITR-TGFbRII ECD, a-DNAM-TGFbRII ECD). In another aspect, the ALT may be any antibody wherein the heavy chain is fused to TGFbRII ECD, and the light chain is fused to another receptor ECD that binds a ligand expressed on tumor cells or the TME (e.g. SIRPa ECD; BTLA ECD, TIM3 ECD, or PD1 ECD, SIGLEC10 ECD). In another aspect the ECD-ECD comprises TGFbRII ECD and another co-stimulatory ligand (e.g. 41BBL, OX40L, GITRL, CD40L, ICOSL). Examples of such ECD-ECDs include (TGFbRII ECD-Fc-41BBL, TGFbRII ECD-Fc-OX40L, TGFbRII ECD-Fc-ICOSL).

In another embodiment, the TGFb/TGFbR binding ALT or ECD-ECD comprises an antibody that binds either CD73 or CD39, fused to TGFbRII ECD (a-CD73-TGFbRII and a-CD39-TGFbRII)

In another aspect, the ALT may be any antibody wherein the heavy chain is fused to TGFbRIIR ECD, and the light chain is fused to another receptor ECD that binds a ligand expressed on tumor cells or the TME (e.g. SIRPa ECD; BTLA ECD, TIM3 ECD, or PD1 ECD, SIGLEC10 ECD).

In one embodiment, an ALT comprises an antibody that binds a TH17-associated cytokine or cytokine receptor fused to a receptor ECD that binds a ligand expressed on tumor cells or the TME. In various examples the additional receptor ECD fused to the heavy or light chain is TGFbRII ECD, VEGFR ECD, PD1 ECD, TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD. In one aspect a first receptor ECD is fused to the heavy chain and a second receptor ECD is fused to the light chain. In another aspect, the ALT may be an antibody wherein the heavy chain is fused to either TGFbRII R ECD or VEGFR ECD, and the light chain is fused to another receptor ECD (e.g. SIRPa ECD; BTLA ECD, TIM3 ECD, or PD1 ECD, SIGLEC10 ECD).

In some embodiments, fusion proteins of the invention disrupt cytokines/cytokine receptor interactions involved in TH17 cell differentiation and function: IL23/IL23R, IL1/IL1R, IL6/IL6R; IL17/IL17R.

In one embodiment the ALT comprises an antibody that binds IL17R, fused to one or more of the following: TGFbRII ECD, VEGFR ECD, PD1 ECD, TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD. Exemplary molecules include anti-IL17R-TGFbRII ECD, anti-IL17R-VEGFR ECD, anti-IL17R-PD1 ECD, anti-IL17R-TIM3 ECD, anti-IL17R-BTLA ECD, anti-IL17R-SIRPa ECD, or anti-IL17R-SIGLEC10 ECD. In one aspect a first receptor ECD is fused to the heavy chain and a second receptor ECD is fused to the light chain. In one aspect, the heavy chain is fused to either TGFbRII or VEGFR ECD, and the light chain is fused to an additional receptor ECD selected from the following PD1 ECD, TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD. Examples of these ALTs include anti-IL17R-TGFbRII ECD-BTLA ECD, anti-IL17R-TGFbRII ECD-PD1 ECD, anti-IL17R-VEGFR ECD-PD1 ECD, anti-IL17R-VEGFR ECD-BTLA ECD, anti-IL17R-BTLA ECD-PD1 ECD, anti-IL17R-BTLA ECD-SIRPa ECD, anti-IL17R-BTLA ECD-TIM3 ECD, anti-IL17R-SIRPa ECD-PD1 ECD.

In one embodiment the ALT comprises an antibody that binds IL23 or IL23R, fused to one or more of the following: TGFbRII ECD, VEGFR ECD, PD1 ECD, TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD. Exemplary molecules include: anti-IL23-TGFbRII ECD, anti-1L23-VEGFR ECD, anti-IL23-PD1 ECD, anti-IL23-TIM3 ECD, anti-IIL23-BTLA ECD, anti-IIL23-SIRPa ECD, or anti-IL23-SIGLEC10 ECD. In one aspect, the heavy chain is fused to either TGFbRII or VEGFR ECD, and the light chain is fused to an additional receptor ECD selected from the following PD1 ECD, TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD. Examples of these ALTs include anti-IL23R-TGFbRII ECD-BTLA ECD, anti-IL23R-TGFbRII ECD-BTLA ECD, anti-IL23R/IL23-TGFbRII ECD-PD1 ECD, anti-IL23R/IL23-VEGFR ECD-BTLA ECD. anti-IL23R/IL23-VEGFR ECD-BTLA ECD, anti-IL123R/IL23-BTLA ECD-PD1 ECD.

In one embodiment the ALT comprises an antibody that binds IL6R or IL6, fused to one or more of the following: TGFbRII ECD, VEGFR ECD, PD1 ECD, TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD. In one embodiment the ALT comprises an antibody that binds IL1R or IL1, fused to one or more of the following: TGFbRII ECD, VEGFR ECD, PD1 ECD, TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD. In one aspect, the heavy chain of the antibody is fused to either TGFbRII or VEGFR ECD, and the light chain is fused to an additional receptor ECD selected from the following PD1 ECD, TIM3 ECD, BTLA ECD, SIRPa ECD, or SIGLEC10 ECD.

The term “treatment” is used interchangeably herein with the term “therapeutic method” and refers to both 1) therapeutic treatments or measures that cure, slow down, lessen symptoms of, and/or halt progression of a diagnosed pathologic conditions or disorder, and 2) and prophylactic/preventative measures. Those in need of treatment may include individuals already having a particular medical disorder as well as those who may ultimately acquire the disorder (i.e., those needing preventive measures).

The term “cancer” refers to a group diseases characterized by abnormal and uncontrolled cell proliferation starting at one site (primary site) with the potential to invade and to spread to others sites (secondary sites, metastases) which differentiate cancer (malignant tumor) from benign tumor. Virtually all the organs can be affected, leading to more than 100 types of cancer that can affect humans. Cancers can result from many causes including genetic predisposition, viral infection, exposure to ionizing radiation, exposure environmental pollutant, tobacco and or alcohol use, obesity, poor diet, lack of physical activity or any combination thereof. As used herein, “neoplasm” or “tumor” including grammatical variations thereof, means new and abnormal growth of tissue, which may be benign or cancerous. In a related aspect, the neoplasm is indicative of a neoplastic disease or disorder, including but not limited, to various cancers. For example, such cancers can include prostate, pancreatic, biliary, colon, rectal, liver, kidney, lung, testicular, breast, ovarian, pancreatic, brain, and head and neck cancers, melanoma, sarcoma, multiple myeloma, leukemia, lymphoma, and the like.

The terms “therapeutically effective amount”, “effective dose,” “therapeutically effective dose”, “effective amount,” or the like refer to that amount of the subject compound that will elicit the biological or medical response of a tissue, system, animal or human that is being sought by the researcher, veterinarian, medical doctor or other clinician.

The terms “administration of” and or “administering” should be understood to mean providing a pharmaceutical composition in a therapeutically effective amount to the subject in need of treatment. Administration routes can be enteral, topical or parenteral. As such, administration routes include but are not limited to intracutaneous, subcutaneous, intravenous, intraperitoneal, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, transdermal, transtracheal, subcuticular, intraarticulare, subcapsular, subarachnoid, intraspinal and intrasternal, oral, sublingual buccal, rectal, vaginal, nasal ocular administrations, as well infusion, inhalation, and nebulization. The phrases “parenteral administration” and “administered parenterally” as used herein means modes of administration other than enteral and topical administration. The pharmaceutical compositions can be administered in a variety of unit dosage forms depending upon the method of administration. Suitable unit dosage forms, include, but are not limited to powders, tablets, pills, capsules, lozenges, suppositories, patches, nasal sprays, injectables, implantable sustained-release formulations, lipid complexes, etc.

In some aspects administration can be in combination with one or more additional therapeutic agents. The phrases “combination therapy”, “combined with” and the like refer to the use of more than one medication or treatment simultaneously to increase the response. The fusion proteins of the present invention might for example be used in combination with other drugs or treatment in use to treat cancer. Specifically the administration of the composition of the present invention to a subject can be in combination with any anti-cancer therapies. Such therapies can be administered prior to, simultaneously with, sequentially with or following administration of the fusion protein of the present invention.

The term “anti-cancer therapy” or “anti-cancer treatment” as used herein is meant to refer to any treatment that can be used to treat cancer, such as surgery, radiotherapy, chemotherapy, immunotherapy, and checkpoint inhibitor therapy.

Examples of chemotherapy include treatment with a chemotherapeutic, cytotoxic or antineoplastic agents including, but not limited to, (i) anti-microtubules agents comprising vinca alkaloids (vinblastine, vincristine, vinflunine, vindesine, and vinorelbine), taxanes (cabazitaxel, docetaxel, larotaxel, ortataxel, paclitaxel, and tesetaxel), epothilones (ixabepilone), and podophyllotoxin (etoposide and teniposide); (ii) antimetabolite agents comprising anti-folates (aminopterin, methotrexate, pemetrexed, pralatrexate, and raltitrexed), and deoxynucleoside analogues (azacitidine, capecitabine, carmofur, cladribine, clofarabine, cytarabine, decitabine, doxifluridine, floxuridine, fludarabine, fluorouracil, gemcitabine, hydroxycarbamide, mercaptopurine, nelarabine, pentostatin, tegafur, and thioguanine); (iii) topoisomerase inhibitors comprising Topoisomerase I inhibitors (belotecan, camptothecin, cositecan, gimatecan, exatecan, irinotecan, lurtotecan, silatecan, topotecan, and rubitecan) and Topoisomerase II inhibitors (aclarubicin, amrubicin, daunorubicin, doxorubicin, epirubicin, etoposide, idarubicinm, merbarone, mitoxantrone, novobiocin, pirarubicin, teniposide, valrubicin, and zorubicin); (iv) alkylating agents comprising nitrogen mustards (bendamustine, busulfan, chlorambucil, cyclophosphamide, estramustine phosphate, ifosamide, mechlorethamine, melphalan, prednimustine, trofosfamide, and uramustine), nitrosoureas (carmustine (BCNU), fotemustine, lomustine (CCNU), N-Nitroso-N-methylurea (MNU), nimustine, ranimustine semustine (MeCCNU), and streptozotocin), platinum-based (cisplatin, carboplatin, dicycloplatin, nedaplatin, oxaliplatin and satraplatin), aziridines (carboquone, thiotepa, mytomycin, diaziquone (AZQ), triaziquone and triethylenemelamine), alkyl sulfonates (busulfan, mannosulfan, and treosulfan), non-classical alkylating agents (hydrazines, procarbazine, triazenes, hexamethylmelamine, altretamine, mitobronitol, and pipobroman), tetrazines (dacarbazine, mitozolomide and temozolomide); (v) anthracyclines agents comprising doxorubicin and daunorubicin. Derivatives of these compounds include epirubicin and idarubicin; pirarubicin, aclarubicin, and mitoxantrone, bleomycins, mitomycin C, mitoxantrone, and actinomycin; (vi) enzyme inhibitors agents comprising FI inhibitor (Tipifarnib), CDK inhibitors (Abemaciclib, Alvocidib, Palbociclib, Ribociclib, and Seliciclib), PrI inhibitor (Bortezomib, Carfilzomib, and Ixazomib), PhI inhibitor (Anagrelide), IMPDI inhibitor (Tiazofurin), LI inhibitor (Masoprocol), PARP inhibitor (Niraparib, Olaparib, Rucaparib), HDAC inhibitor (Belinostat, Panobinostat, Romidepsin, Vorinostat), and PIKI inhibitor (Idelalisib); (vii) receptor antagonist agent comprising ERA receptor antagonist (Atrasentan), Retinoid X receptor antagonist (Bexarotene), Sex steroid receptor antagonist (Testolactone); (viii) ungrouped agent comprising Amsacrine, Trabectedin, Retinoids (Alitretinoin Tretinoin) Arsenic trioxide, Asparagine depleters (Asparaginase/Pegaspargase), Celecoxib, Demecolcine Elesclomol, Elsamitrucin, Etoglucid, Lonidamine, Lucanthone, Mitoguazone, Mitotane, Oblimersen, Omacetaxine mepesuccinate, and Eribulin.

Examples of immunotherapy include treatment with antibodies including, but not limited to, alemtuzumab, Avastin (bevacizumab), Bexxar (tositumomab), CDP 870, and CEA-Scan (arcitumomab), denosumab, Erbitux (cetuximab), Herceptin (trastuzumab), Humira (adalimumab), IMC-IIF 8, LeukoScan (sulesomab), MabCampath (alemtuzumab), MabThera (Rituximab), matuzumab, Mylotarg (gemtuzumab oxogamicin), natalizumab, NeutroSpec (Technetium (99mTc) fanolesomab), panitumamab, Panorex (Edrecolomab), ProstaScint (Indium-Ill labeled Capromab Pendetide), Raptiva (efalizumab), Remicade (infliximab), ReoPro (abciximab), rituximab, Simulect (basiliximab), Synagis (palivizumab), TheraCIM hR3, tocilizumab, Tysabri (natalizumab), Verluma (nofetumomab), Xolair (omalizumab), Zenapax (dacliximab), Zevalin (ibritumomab tiuxetan (IDEC-Y2B8) conjugated to yttrium 90), Gilotrif (afatinib), Lynparza (olaparib), Perj eta (pertuzumab), Otdivo (nivolumab), Bosulif (bosutinib), Cabometyx (cabozantinib), trastuzumab-dkst (Ogivri), Sutent (sunitinib malate), Adcetris (brentuximab vedotin), Alecensa (alectinib), Calquence (acalabrutinib), Yescarta (ciloleucel), Verzenio (abemaciclib), Keytruda (pembrolizumab), Aliqopa (copanlisib), Nerlynx (neratinib), Imfinzi (durvalumab), Darzalex (daratumumab), Tecentriq (atezolizumab), and Tarceva (erlotinib).

“Checkpoint inhibitor therapy” is a form of cancer treatment that uses immune checkpoints which affect immune system functioning. Immune checkpoints can be stimulatory or inhibitory. Tumors can use these checkpoints to protect themselves from immune system attacks. Checkpoint therapy can block inhibitory checkpoints, restoring immune system function. Checkpoint proteins include programmed cell death 1 protein (PDCD1, PD-1; also known as CD279) and its ligand, PD-1 ligand 1 (PD-L1, CD274), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), A2AR (Adenosine A2A receptor), B7-H3 (or CD276), B7-H4 (or VTCN1), BTLA (B and T Lymphocyte Attenuator, or CD272), IDO (Indoleamine 2,3-dioxygenase), MR (Killer-cell Immunoglobulin-like Receptor), LAG3 (Lymphocyte Activation Gene-3), TIM-3 (T-cell Immunoglobulin domain and Mucin domain 3), and VISTA (V-domain Ig suppressor of T cell activation).

In some embodiments the fusion proteins may be used in in combination with another therapy including surgery, chemotherapy, radiation therapy, targeted small molecules, anti-angiogenic therapy or immunotherapy. In certain embodiments the fusion protein is administered with another fusion protein. Immunotherapy may include any immuno-oncologic drug selected from a broad range of agents, including antibodies, vaccines, adjuvant therapies, cytokines, oncolytic viruses, bispecific molecules, and cellular therapies. In a specific embodiment, the molecules of the invention may be administered to a subject in combination with (Chimeric Antigen Receptor (CAR) T cell therapy.

In one embodiment, the present invention provides for compositions comprising the previously described molecule or fusion protein and a pharmaceutical carrier.

In an additional embodiment, the present invention provides a method of treating a subject having cancer comprising administering to the subject the previously described molecules, fusion proteins or compositions. In one aspect, the molecule, fusion protein or composition is administered by intracutaneous, subcutaneous, intravenous, intraperitoneal, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, transdermal, transtracheal, subcuticular, intraarticulare, subcapsular, subarachnoid, intraspinal and intrasternal, oral, sublingual buccal, rectal, vaginal, nasal or ocular administrations, by infusion, inhalation, or nebulization or by parenteral administration.

The molecules of the invention may be used in conjunction or in combination with any other type of therapy including surgery, chemotherapy, radiation therapy, targeted small molecules, anti-angiogenic therapy or immunotherapy. Immunotherapy may include any immuno-oncologic drug selected from a broad range of agents, including antibodies, fusion proteins, vaccines, adjuvant therapies, cytokines, oncolytic viruses, bispecific molecules, and cellular therapies. In a specific embodiment, the molecules of the invention may be administered to a subject in combination with (Chimeric Antigen Receptor (CAR) T cell therapy. In various aspects, the molecules of the invention may be administered prior to, concurrently, sequentially, and/or following any other type of said therapy. In various aspects, the molecules of the invention may be administered in a composition with any other therapeutic agent.

In some embodiments, fusion proteins described in the invention and combination therapies counteract immune dysfunction in the tumor microenvironment. In some embodiments, fusion proteins described in the invention and combination therapies counteract angiogenesis in the tumor microenvironment.

In various embodiments, a subject may be administered one or more fusion proteins described in the invention in combination with a polypeptide that disables an immune cell inhibitory molecule or T cell co-inhibitory molecule (e.g., CTLA-4, BTLA, TIM-3, CEACAM1, or CEACAM-5, TIGIT, PVRIG, VISTA, VSIG8, LAG-3, CD47, SIRPa, CD24, SIGLEC10, or LILRB1). In some embodiments, this polypeptide is an antibody. In other embodiments, the polypeptide is a fusion protein comprising the ECD of a T cell co-inhibitory molecule. In some embodiments, this polypeptide may be PD1-Fc, TIM3-Fc, or BTLA-Fc. In some embodiments, the polypeptide may be an anti-PD1/anti-PDL1 mAb. Exemplary such antibodies are anti-PD1 (e.g., nivolumab, pembrolizumab) and anti-PDL1 (e.g., durvalumab, avelumab, atezolizumab).

In various embodiments, a subject may be administered one or more fusion proteins described in the invention in combination with a chimeric antigen receptor T cell (CAR T cell)

In various embodiments, a subject may be administered one or more fusion proteins described in the invention in combination with an immunotherapeutic agent.

Any VEGF or VEGFR-binding fusion protein of the invention may be used for the treatment of cancer. Any TGFb/TGFbR-inhibiting fusion protein of the invention may be used for the treatment of cancer. Any fusion protein of the invention that interrupts a cytokine/cytokine receptor interaction involved in TH17 cell differentiation or function may be used for the treatment of cancer. In some embodiments, this cytokine/cytokine receptor interaction involved in TH17 inhibition is selected from IL23/IL23R, IL1/IL1R, IL6/IL6R, or IL17/IL17R.

In one embodiment, a VEGF or VEGFR-binding fusion protein of the invention may be used in combination with a TGF/TGFbR-inhibiting fusion protein of the invention for the treatment of cancer.

In another embodiment, a VEGF or VEGFR-binding fusion protein of the invention may be used in combination with a TGFb/TGFbR inhibitor for the treatment of cancer. In some aspects, this TGFb/TGFbR inhibitor is selected from: a-TGFb antibody; a-TGFbR antibody; TGFbRII ECD containing fusion protein (e.g. TGFbRIIecd-Fc); TGFbR TKI (e.g. galunisertib); anti-GARP antibody; anti-LAP antibody; ALT comprising TGFbRII ECD.

In another embodiment, a TGFb/TGFbR-inhibiting fusion protein of the invention may be used in combination with a VEGF/VEGFR inhibitor for the treatment of cancer. In some aspects, the VEGF/VEGFR inhibitor may be selected from: anti-VEGF antibody (e.g., bevacizumab), anti-VEGFR antibody (e.g. ramucirumab), VEGFR kinase inhibitor (e.g., sunitinib, sorafenib, axitinib, cabozantinib, regorafenib, pazopanib, vandetanib, lenvatenib), or VEGFR ECD-Fc fusion protein (e.g., aflibercept).

In another embodiment, a VEGF/VEGFR-inhibiting fusion protein of the invention may be used in combination with a fusion protein of the invention that counteracts TH17 differentiation or function for the treatment of cancer.

In another embodiment, a VEGF or VEGFR-binding fusion protein of the invention may be used in combination with an agent that counteracts TH17 differentiation or function for the treatment of cancer. In some aspects, this agent is an inhibitor of the interaction between IL23/IL23R, IL1/IL1R, IL6/IL6R, or IL17/IL17R. In some aspects, this agent is selected from: anti-IL17R antibody, anti-IL17 antibody, anti-IL17 nanobody; anti-IL6R antibody, anti-IL6 antibody; IL23 antibody, anti-IL23R antibody; anti-IL1R antibody, anti-IL1 antibody.

In another embodiment, a TGFb/TGFbR-inhibiting fusion protein of the invention may be used in combination with a fusion protein of the invention that counteracts TH17 differentiation or function for the treatment of cancer.

In another embodiment, a TGFb/TGFbR-inhibiting fusion protein of the invention may be used in combination with an agent that counteracts TH17 differentiation or function for the treatment of cancer. In some aspects, this agent is an inhibitor of the interaction between IL23/IL23R, IL1/IL1R, IL6/IL6R, or IL17/IL17R. In some aspects, this agent is selected from: anti-IL17R antibody, anti-IL17 antibody, anti-IL17 nanobody; anti-IL6R antibody, anti-IL6 antibody; IL23 antibody, anti-IL23R antibody; anti-IL1R antibody, anti-IL1 antibody.

In another embodiment, a fusion protein of the invention that counteracts TH17 differentiation or function may be used in combination with a TGFb/TGFbR inhibitor for the treatment of cancer. In some aspects, this TGFb/TGFbR inhibitor is selected from: a-TGFb antibody; a-TGFbR antibody; TGFbRII ECD containing fusion protein (e.g. TGFbRIIecd-Fc); TGFbR TKI (e.g. galunisertib); anti-GARP antibody; anti-LAP antibody; ALT comprising TGFbRII ECD.

In another embodiment, a fusion protein of the invention that counteracts TH17 differentiation or function may be used in combination with a VEGF/VEGFR inhibitor for the treatment of cancer. In some aspects, the VEGF/VEGFR inhibitor may be selected from: anti-VEGF antibody (e.g., bevacizumab), anti-VEGFR antibody (e.g. ramucirumab), VEGFR kinase inhibitor (e.g., sunitinib, sorafenib, axitinib, cabozantinib, regorafenib, pazopanib, vandetanib, lenvatenib), or VEGFR ECD-Fc fusion protein (e.g., aflibercept).

In another embodiment, a TGFb/TGFbR-inhibiting fusion protein of the invention may be used in combination with an agent that inhibits the interaction of CD47 and SIRPa. In some aspects, the CD47/SIRPa inhibitor may be selected from: a-CD47 mAb (e.g., magrolimab), a-SIRPa mAb, SIRPa containing fusion protein (e.g., SIRPa-Fc). In another aspect, the agent that inhibits the interaction of CD47 and SIRPa is a fusion protein of the invention.

In another embodiment, a VEGF/VEGFR-binding fusion protein of the invention may be used in combination with an agent that inhibits the interaction of CD47 and SIRPa. In some aspects, the CD47/SIRPa inhibitor may be selected from: a-CD47 mAb (e.g., magrolimab), a-SIRPa mAb, or SIRPa containing fusion protein (e.g., SIRPa-Fc). In another aspect, the agent that inhibits the interaction of CD47 and SIRPa is a fusion protein of the invention.

In another embodiment, a fusion protein of the invention that counteracts TH17 differentiation or function may be used in combination with an agent that inhibits the interaction of CD47 and SIRPa. In some aspects, the CD47/SIRPa inhibitor may be selected from: a-CD47 mAb (e.g., magrolimab), a-SIRPa mAb, or SIRPa containing fusion protein (e.g., SIRPa-Fc). In another aspect, the agent that inhibits the interaction of CD47 and SIRPa is a fusion protein of the invention.

In another embodiment, a CD47/SIRPa-binding fusion protein of the invention may be used in combination with a TGFb/TGFbR inhibitor for the treatment of cancer. In some aspects, this TGFb/TGFbR inhibitor is selected from: a-TGFb antibody; a-TGFbR antibody; TGFbRII ECD containing fusion protein (e.g. TGFbRIIecd-Fc); TGFbR TKI (e.g. galunisertib); anti-GARP antibody; anti-LAP antibody; ALT comprising TGFbRII ECD. In one embodiment, a-CD73-TGFbRII is combined with anti-CD47 or SIRPa-Fc for the treatment of cancer. In one aspect, the anti-CD47 polypeptide is magrolimab.

In another embodiment, a CD47/SIRPa-binding fusion protein of the invention may be used in combination with a VEGF/VEGFR inhibitor for the treatment of cancer. In some aspects, the VEGF/VEGFR inhibitor may be selected from: anti-VEGF antibody (e.g., bevacizumab), anti-VEGFR antibody (e.g. ramucirumab), VEGFR kinase inhibitor (e.g., sunitinib, sorafenib, axitinib, cabozantinib, regorafenib, pazopanib, vandetanib, lenvatenib), or VEGFR ECD-Fc fusion protein (e.g., aflibercept).

In another embodiment, a CD47/SIRPa-binding fusion protein of the invention may be used in combination with an agent that counteracts TH17 differentiation or function for the treatment of cancer. In some aspects, this agent is an inhibitor of the interaction between IL23/IL23R, IL1/IL1R, IL6/IL6R, or IL17/IL17R. In some aspects, this agent is selected from: anti-IL17R antibody, anti-IL17 antibody, anti-IL17 nanobody; anti-IL6R antibody, anti-IL6 antibody; IL23 antibody, anti-IL23R antibody; anti-IL1R antibody, anti-IL1 antibody.

In one embodiment, a polypeptide that simultaneously binds VEGF and a component of the tumor microenvironment is combined with a polypeptide that simultaneously binds TGFb and a component of the tumor microenvironment. In various aspects, the component of the tumor microenvironment may be a tumor cell surface molecule. In another aspect, the component of the tumor microenvironment may be a immune cell surface molecule associated with tumor-infilitrating T cells such as TH17 cells (e.g., IL-23R) or Tregs (e.g., CTLA-4).

In some embodiments, a fusion protein described in the invention that inhibits TGFb/TGFbR is used for treatment of cancer in combination with a fusion protein described in the invention that inhibits one or more of: PD1/PDL1, CD47/SIRPa, BTLA/HVEM, TIM3/CEACAM, VEGF/VEGFR, SIGLEC10/CD24. In some embodiments, a fusion protein described in the invention that inhibits PD1/PDL1 is used for treatment of cancer in combination with a fusion protein described in the invention that inhibits one or more of: TGFb/TGFbR, CD47/SIRPa, BTLA/HVEM, TIM3/CEACAM, VEGF/VEGFR, SIGLEC10/CD24. In some embodiments, a fusion protein described in the invention that inhibits CD47/SIRPa is used for treatment of cancer in combination with a fusion protein described in the invention that inhibits one or more of: TGFb/TGFbR, PD1/PDL1, BTLA/HVEM, TIM3/CEACAM, VEGF/VEGFR, SIGLEC10/CD24. In some embodiments, a fusion protein described in the invention that inhibits BTLA/HVEM is used for treatment of cancer in combination with a fusion protein described in the invention that inhibits one or more of: TGFb/TGFbR, CD47/SIRPa, PD1/PDL1, TIM3/CEACAM, VEGF/VEGFR, SIGLEC10/CD24. In some embodiments, a fusion protein described in the invention that inhibits TIM3/CEACAM is used for treatment of cancer in combination with a fusion protein described in the invention that inhibits one or more of: TGFb/TGFbR, CD47/SIRPa, BTLA/HVEM, PD1/PDL1, VEGF/VEGFR, SIGLEC10/CD24. In some embodiments, a fusion protein described in the invention that inhibits VEGF/VEGFR is used for treatment of cancer in combination with a fusion protein described in the invention that inhibits one or more of: TGFb/TGFbR, CD47/SIRPa, BTLA/HVEM, TIM3/CEACAM, PD1/PDL1, SIGLEC10/CD24. In some embodiments, a fusion protein described in the invention that inhibits SIGLEC10/CD24 is used for treatment of cancer in combination with a fusion protein described in the invention that inhibits one or more of: TGFb/TGFbR, CD47/SIRPa, BTLA/HVEM, TIM3/CEACAM, VEGF/VEGFR, PD1/PDL1.

Sequences of the components and fusion proteins of the invention are in Table 1

TABLE 1

Sequence

SEQ ID NO: 1
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQSPEKGLEWIGEI

anti-41BB
NHGGYVTYNPSLESRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDYGPG

antibody
NYDWYFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD

(urelumab) -
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTC

heavy chain
NVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK

SEQ ID NO: 2
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDAS

anti-41BB
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPALTFCGGT

antibody
KVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA

(urelumab) - light
LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP

chain
VTKSFNRGEC

SEQ ID NO: 3
EVQLVESGGGLVQPGGSLRLSCAASGYSITNDYAWNWVRQAPGKGLEWV

anti-CA125
GYISYSGYTTYNPSLKSRFTISRDTSKNTLYLQMNSLRAEDTAVYYCARWT

antibody (ab1) -
SGLDYWGQGTLVTVSSCSTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

heavy chain
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 4
DIQMTQSPSSLSASVGDRVTITCKASDLIHNWLAWYQQKPGKAFKLLIYGA

anti-CA125
TSLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYWTTPFTFGQGTK

antibody (ab1) -
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLENFYPREAKVQWKVDNAL

light chain
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSFV

TKSFERGEC

SEQ ID NO: 5
EVQLVESGGGLVQPGGSLRLSCAASGYSITNDYAWNWVRQAPGKGLEWV

anti-CA125
GYISYSGYTTYNPSLKSRFTISRDTSKNTLYLQMNSLRAEDTAVYYCARWT

antibody
SGLDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

(sofituzumab) -
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

heavy chain
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 6
DIQMTQSPSSLSASVGDRVTITCKASDLIHNWLAWYQQKPGKAPKLLIYGA

anti-CA125
TSLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYWTTPFTFGQGTK

antibody
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

(sofituzumab) -
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

light chain
TKSFNRGEC

SEQ ID NO: 7
QVQLVESGGGSVQPGRSLRLSCEASGFTFEAYAMHWVRQPPGKGLEWVSS

anti-CA19-9
INWNSGRIAYADSVKGRFTISRDNARNSLYLQMNSLRLEDTAFYYCAKDIR

antibody (MVT-
RFSTGGAEFEYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV

5873) - heavy
KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY

chain
ICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 8
QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNFVYWYQQLPGTAPKLLIYRN

anti-CA19-9
NQRPSGVPDRFSGSRSGTSASLAISGLRSEDEADYYCAAWDDSLGGHYVFG

antibody (MVT-
TGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWK

5873) - light chain
ADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGS

TVEKTVAPTECS

SEQ ID NO: 9
QVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGRGLEWIG

anti-CD20
AIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARST

antibody
YYGGDWYFNVWGAGTTVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLV

(rituximab) -
KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY

heavy chain
ICNVNHKPSNTKVDKKAEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 10
QIVLSQSPAILSASPGEKVTMTCRASSSVSYIHWFQQKPGSSPKPWIYATSNL

anti-CD20
ASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLEI

antibody
KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG

(rituximab) - light
NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS

chain
FNRGEC

SEQ ID NO: 11
QIQLQQSGPEVVKPGASVKISCKASGYTFTDYYITWVKQKPGQGLEWIGWI

anti-CD30
YPGSGNTKYNEKFKGKATLTVDTSSSTAFMQLSSLTSEDTAVYFCANYGN

antibody
YWFAYWGQGTQVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

(brentuximab) -
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

heavy chain
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

SEQ ID NO: 12
DIVLTQSPASLAVSLGQRATISCKASQSVDFDGDSYMNWYQQKPGQPPKV

anti-CD30
LIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPWTF

antibody
GGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK

(brentuximab) -
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ

light chain
GLSSPVTKSFNRGEC

SEQ ID NO: 13
QVQLQQSGAELAKPGASVKMSCKASGYTFTSYRMHWVKQRPGQGLEWIG

anti-CD33
YINPSTGYTEYNQKFKDKATLTADKSSSTAYMQLSSLTFEDSAVYYCARGG

antibody
GVFDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

(gemtuzumab) -
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

heavy chain
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD

ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 14
DIQMTQSPSTLSASVGDRVTITCRASQSINTWLAWYQQKPGKAPKLLMYK

anti-CD33
ASSLESGVPSRFIGSGSGTEFTLTISSLQPDDFATYYCQQYNSDSKMFGQGT

antibody
KVEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDN

(gemtuzumab) -
ALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS

light chain
PVTKSFNRGEC

SEQ ID NO: 15
EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSA

anti-CD38
ISGSGGGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKI

antibody
LWFGEPVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

(daratumumab) -
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

heavy chain
CNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 16
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDAS

anti-CD38
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKV

antibody
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

(daratumumab) -
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

light chain
KSFNRGEC

SEQ ID NO: 17
QVOLVOSGSELKKPGASVKVSCKASGYTFTHYGMNWVRQAPGQGLKWM

anti-CD39
GWINTYTGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCARR

antibody
RYEGNYVFYYFDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

(IPH5201) - heavy
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

chain
TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 18
DIQMTQSPSSLSASVGDRVTITCRASENIYSYFSWYOQKPGKAPKLLIYTAK

anti-CD39
TLAEGVPSRFSGSGSGTDFTLTISSLOPEDFATYYCQHHYVTPYTFGGGTKV

antibody
EIKRTVAAPSVFIFPPSDEOLKSGTASVVCLLNNFYPREAKVOWKVDNAL0

(IPH5201) - light
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHOGLSSPVT

chain
KSFNRGEC

SEQ ID NO: 19
EVQLQESGPGLVKPSETLSLTCTVSGYSITSNYYWNWIRQPPGKGLEWMG

anti-CD40
YIRYDGSNNYNPSLKNRVTISRDTSKNQFSLKLSSVTAADTAVYYCARLDY

antibody (ABBV-
WGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS

428) - heavy chain
WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT

KVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH

QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKN

QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV

DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 20
DAVMTQTPLSLSVTPGQPASISCRSSQSLENTNGNTFLNWYLQKPGQSPQL

anti-CD40
LIYRVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCLQVTHVPFTF

antibody (ABBV-
GQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK

428) - light chain
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ

GLSSPVTKSFNRGEC

SEQ ID NO: 21
QVQLQQPGAELVKPGASVMMSCKASGYTFTNYNMHWVKQTPGQGLEWI

anti-CD47
GTIYPGNDDTSYNQKFKDKATLTADKSSSAAYMQLSSLTSEDSAVYYCAR

antibody (5F9) -
GGYRAMDYWGQTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

heavy chain
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 22
DVLMTQTPLSLPVSLGDQASISCRSSQSIVYSNGNTYLGWYLQKPGQSPKL

anti-CD47
LIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYHCFQGSHVPYTF

antibody (5F9) -
GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK

light chain
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ

GLSSPVTKSFNRGEC

SEQ ID NO: 23
EVQLVQSGAEVKKPGESLKISCKASGYAFSSSWINWVRQMPGKGLEWMG

anti-CD73
RIYPRAGDTNYAGKFKDQVTISADKSISTAYLQWSSLKASDTAMYYCASLL

antibody
DYSMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

(GS1423) - heavy
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

chain
NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 24
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTS

anti-CD73
RLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPLTFGQGTKVE

antibody
IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS

(GS1423) - light
GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK

chain
SFNRGEC

SEQ ID NO: 25
EVQLVESGGGVVQPGRSLRLSCSASGFDFTTYWMSWVRQAPGKGLEWIGE

anti-CEACAM5
IHPDSSTINYAPSLKDRFTISRDNAKNTLFLQMDSLRPEDTGVYFCASLYFGF

antibody
PWFAYWGQGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

(labetuzumab) -
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

heavy chain
KPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

DIQLTQSPSSLSASVGDRVTITCKASQDVGTSVAWYQQKPGKAPKLLIYWT

SEQ ID NO: 26
STRHTGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYSLYRSFGQGTKVE

anti-CEACAM5
IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS

antibody
GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK

(labetuzumab) -
SFNRGEC

light chain

SEQ ID NO: 27
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVT

anti-CTLA4
FISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTG

antibody
WLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

(ipilimumab) -
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

heavy chain
NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQ

SEQ ID NO: 28
EIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQKPGQAPRLLIYGA

anti-CTLA4
FSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTK

antibody
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

(ipilimumab) -
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

light chain
TKSFNRGEC

SEQ ID NO: 29
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGMNWVRQAPGQGLEWM

anti-DLL3
GWINTYTGEPTYADDFKGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCAR

antibody
IGDSSPSDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

(rovalpituzumab) -
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

heavy chain
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

SEQ ID NO: 30
EIVMTQSPATLSVSPGERATLSCKASQSVSNDVVWYQQKPGQAPRLLIYYA

anti-DLL3
SNRYTGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQDYTSPWTFGQGTK

antibody
LEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

(rovalpituzumab) -
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

light chain
TKSFNRGEC

SEQ ID NO: 31
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anti-DLL4
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

antibody (ABT-
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

165) - heavy chain
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPK

PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 32
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTS

anti-DLL4
SLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKV

antibody (ABT-
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

165) - light chain
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGEC

SEQ ID NO: 33
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYWIEWVRQAPGQGLEWMG

anti -DPEP3
EILPGSGNTYYNERFKDRVTITADESTSTAYMELSSLRSEDTAVYYCARRA

antibody (ab1) -
AAYYSNPEWFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL

heavy chain
VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT

YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKD

TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST

YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY

TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS

DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

SEQ ID NO: 34
EIVLTQSPATLSLSPGERATLSCTASSSVNSFYLHWYQQKPGLAPRLLIYSTS

anti-DPEP3
NLASGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCHQYHRSPYTFGQGTKL

antibody (ab1) -
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

light chain
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGEC

SEQ ID NO: 35
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYWIEWVRQAPGQGLEWMG

anti-DPEP3
EILPGSGNTYYNERFKDRVTITADESTSTAYMELSSLRSEDTAVYYCARRA

antibody (ab2) -
AAYYSNPEWFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL

heavy chain
VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT

YICNVNHKPSNTKVDKKVEPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKD

TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST

YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY

TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS

DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

SEQ ID NO: 36
QVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYYWTWIRQSPGKGLEWIG

anti-EGFR
HIYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTG

antibody
AFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV

(panitumumab) -
TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHK

heavy chain
PSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVH

QDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKN

QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTV

DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 37
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDA

anti-EGFR
SNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLPLAFGGGTKV

antibody
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

(panitumumab) -
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

light chain
KSFNRGEC

SEQ ID NO: 38
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGDYYWSWIRQPPGKGLEWIG

anti-EGFR
YIYYSGSTDYNPSLKSRVTMSVDTSKNQFSLKVNSVTAADTAVYYCARVSI

antibody
FGVGTFDYWGQGTLVTVSSASTKGPSVLPLAPSSKSTSGGTAALGCLVKDY

(necitumumab) -
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

heavy chain
VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 39
EIVMTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDAS

anti-EGFR
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCHQYGSTPLTFGGGTKA

antibody
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

(necitumumab) -
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

light chain
KSFNRGEC

SEQ ID NO: 40
EVQLQESGPGLVKPSQTLSLTCTVSGYSISNDFAWNWIRQLPGKGLEWMG

anti-EGFR
YISYKGNTRYQPSLKSRITISRDTSKNQFFLKLNSVTAADTATYYCVTASRG

antibody (ABBV-
LPYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV

321) - heavy chain
TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP

SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 41
DIQMTQSPSSMSVSVGDRVTITCHSSQDITYNIGWLQQKPGKSFKGLIYHGA

anti-EGFR
NLDDGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCVQYDEFPWTFGGGTK

antibody (ABBV-
LEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

321) - light chain
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGEC

SEQ ID NO: 42
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

antibody
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

(cetuximab) -
EPVTVSWNSGALTSGVHTFYAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

heavy chain
HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 43
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES

anti-EGFR
ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK

antibody
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

(cetuximab) - light
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

chain
NRGEC

SEQ ID NO: 44
DVQLQESGPGLVKPSQSLSLTCTVTAYSVTSDYAWNWIRQFPGNKLEWMG

anti-EGFRvIII
YISYSGTTRYNPSLKSRISITRDTSKNQFFLQLNSMTAEDTATYYCSRQGRG

antibody (ab1) -
FPYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV

heavy chain
TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP

SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 45
DILMTQSPSSMSVSLGDTVSITCHASQDINSNIGWLQQKPGKSFKGLIYHGT

anti-EGFRvIII
NLEDGVPSRFSGSGSGADYSLTISSLESEDFADYYCVQYAQFPWTFGGGTK

antibody (ab1) -
LEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

light chain
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGEC

SEQ ID NO: 46
QVQLQESGPGLVKPSQTLSLTCTVSGYSISSDFAWNWIRQPPGKGLEWMG

anti-EGFRvIII
YISYSGNTRYQPSLKSRITISRDTSKNQFFLKLNSVTAADTATYYCVTAGRG

antibody
FPYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV

(depatuxizumab) -
TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP

heavy chain
SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 47
DIQMTQSPSSMSVSVGDRVTITCHSSQDINSNIGWLQQKPGKSFKGLIYHGT

anti-EGFRvIII
NLDDGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCVQYAQFPWTFGGGTK

antibody
LEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

(depatuxizumab) -
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

light chain
TKSFNRGEC

SEQ ID NO: 48
QVQLVQPGAEVRKPGASVKVSCKASGYRFTSYYIDWVRQAPGQGLEWMG

anti-GARP
RIDPEDAGTKYAQKFQGRVTMTADTSTSTVYVELSSLRSEDTAVYYCARY

antibody (ARGX-
EWETVVVGDLMYEYEYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTA

115) - heavy chain
ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPK

PKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQ

VYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG

SEQ ID NO: 49
DIQMTQSPSSLSASVGDRVTITCQASQSISSYLAWYQQKPGQAPKILIYGAS

anti-GARP
RLKTGVPSRFSGSGSGTSFTLTISSLEPEDAATYYCQQYASVPVTFGQGTKV

antibody (ARGX-
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

115) - light chain
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGEC

SEQ ID NO: 50
EVQLLQSGPELEKPGASVMISCKASGSSFTGYNMNWVRQNIGKSLEWIGAI

anti-GD2
DPYYGGTSYNQKFKGRATLTVDKSSSTAYMHLKSLTSEDSAVYYCVSGME

antibody
YWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV

(dinutuximab) -
SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN

heavy chain
TKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL

HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

EIVMTQSPATLSVSPGERATLSCRSSQSLVHRNGNTYLHWYLQKPGQSPKL

SEQ ID NO: 51
LIHKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHVPPLTF

anti-GD2
GAGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK

antibody
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ

(dinutuximab) -
GLSSPVTKSFNRGEC

light chain

SEQ ID NO: 52
EVQLVESGGGLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLEWVA

anti-HER2
DVNPNSGGSIYNQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYYCARN

antibody
LGPSFYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

(pertuzumab) -
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

heavy chain
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

SEQ ID NO: 53
DIQMTQSPSSLSASVGDRVTITCKASQDVSIGVAWYQQKPGKAPKLLIYSAS

anti-HER2
YRYTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYIYPYTFGQGTKV

antibody
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

(pertuzumab) -
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

light chain
KSFNRGEC

SEQ ID NO: 54
EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVAR

anti-HER2
IYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWG

antibody
GDGFYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

(trastuzumab) -
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

heavy chain
CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 55
DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSA

anti-HER2
SFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKV

antibody
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

(trastuzumab) -
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

light chain
KSFNRGEC

SEQ ID NO: 56
QVQLQESGPGLVKPSETLSLTCTVSGGSISIYYWSWIRQPPGKGLEWIGYVY

anti-HGF
YSGSTNYNPSLKSRVTISVDTSKNQFSLKLNSVTAADTAVYYCARGGYDF

antibody
WSGYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYF

(rilotumumab) -
PEPVTVSWNSGALTSGVHTFYAVLQSSGLYSLSSVVTVPSSNFGTQTYTCN

heavy chain
VDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTP

EVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 57
EIVMTQSPATLSVSPGERATLSCRASQSVDSNLAWYRQKPGQAPRLLIYGA

anti-HGF
STRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYINWPPITFGQGTR

antibody
LEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

(rilotumumab) -
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

light chain
TKSFNRGEC

SEQ ID NO: 58
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDYAMHWVRQAPGQGLEWM

anti-ICOS
GLISTYSDHTNYNQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCGRN

antibody
NYGNYGWYFDVWGQGTTVTVSS

(GSK3359609) -

heavy chain

SEQ ID NO: 59
EIVLTQSPATLSLSPGERATLSCSASSSVSYMHWYQQKPGQAPRLLIYDTSK

anti-ICOS
LASGIPARFSGSGSGTDYTLTISSLEPEDFAVYYCFQGSGYPYTFGOGTKLEI

antibody
KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG

(G5K3359609) -
NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS

light chain
FNRGEC

SEQ ID NO: 60
QVQLQQPGAELVRPGASVKLSCKASGYTFSNYLMNWVKQRPEQDLDWIG

anti-IL13Ra2
RIDPYDGDIDYNQNFKDKAILTVDKSSSTAYMQLSSLTSEDSAVYYCARGY

antibody (ab1) -
GTAYGVDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

heavy chain
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 61
DIVLTQSPASLAVSLGQRATISCRASESVDNYGISFMNWFQQKPGQPPKLLI

anti-IL13Ra2
YAASRQGSGVPARFSGSGSGTDFSLNIHPMEEDDTAMYFCQQSKEVPWTF

antibody (ab1) -
GGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK

light chain
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ

GLSSPVTKSFNRGEC

SEQ ID NO: 62
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

antibody
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

(brodalumab) -
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

heavy chain
DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 63
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWFQQKPGQAPRPLIYDAS

anti-IL17R
TRATGVPARFSGSGSGTDFTLTISSLQSEDFAVYYCQQYDNWPLTFGGGTK

antibody
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

(brodalumab) -
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

light chain
TKSFNRGEC

SEQ ID NO: 64
EVQLVQSGAEVKKPGASVKVSCKASGYTFKYYGMNWVRQAPGQGLERM

anti-IL1a
GWINTYTGQSTYADDFKGRVTFTLDTSTSTAYMELSSLRSEDTAVYYCAR

antibody
DIYYYGSDFAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

(3D12r16) - heavy
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

chain
TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 65
DIQMTQSPSSLSASVGDRVTITCRASQDISNMLNWYQQKPGKAPKLLIYYT

anti-IL1a
SRLKPGVPSRFSGSGSGTDYTFTISSLQPEDIATYFCQQGKTAPYTFGQGTKL

antibody
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

(3D12r16) - light
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

chain
KSFNRGEC

SEQ ID NO: 66
EVQLVESGGGVVQPGRSLRLSCSASGFIFSRYDMSWVRQAPGKGLEWVAY

anti-IL1b
ISHGGAGTYYPDSVKGRFTISRDNSKNTLFLQMDSLRAEDTAVYYCARGG

antibody (E26.35)
VYKGYFDVWGQGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

- heavy chain
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 67
DIQMTQSPSSLSASVGDRVTITCRASGNIHNYLTWYQQTPGKAPKLLIYNA

anti-IL1b
KTLADGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQHFWSIPYTFGQGTK

antibody (E26.35)
LQITRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

- light chain
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGEC

SEQ ID NO: 68
QVQLVESGGGVVQPGRSLRLSCAASGFTFSVYGMNWVRQAPGKGLEWVA

anti-IL1b
IIWYDGDNQYYADSVKGRFTISRDNSKNTLYLQMNGLRAEDTAVYYCARD

antibody
LRTGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

(canakinumab) -
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

heavy chain
VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 69
EIVLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLIKYASQ

anti-IL1b
SFSGVPSRFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPFTFGPGTKVDI

antibody
KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG

(canakinumab) -
NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS

light chain
FNRGEC

SEQ ID NO: 70
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVA

anti-IL23
VIWYDGSNEYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARD

antibody
RGYTSSWYPDAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALG

(brazikumab) -
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFG

heavy chain
TQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKD

TLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNST

FRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVY

TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDS

DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 71
QSVLTQPPSVSGAPGQRVTISCTGSSSNTGAGYDVHWYQQVPGTAPKLLIY

anti-IL23
GSGNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSGWVF

antibody
GGGTRLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAW

(brazikumab) -
KADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHE

light chain
GSTVEKTVAPTECS

SEQ ID NO: 72
EVQLVQSGAEVKKPGESLKISCKGSGYSFSNYWIGWVRQMPGKGLEWMGI

anti-IL23
IDPSNSYTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCARWYY

antibody
KPFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

(guselkumab) -
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

heavy chain
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD

ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 73
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGSGYDVHWYQQLPGTAPKLLIYG

anti-IL23
NSKRPSGVPDRFSGSKSGTSASLAITGLQSEDEADYYCASWTDGLSLVVFG

antibody
GGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWK

(guselkumab) -
ADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGS

light chain
TVEKTVAPTECS

SEQ ID NO: 74
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDQTIHWMRQAPGQGLEWIG

anti-IL23
YIYPRDDSPKYNENFKGKVTITADKSTSTAYMELSSLRSEDTAVYYCAIPDR

antibody
SGYAWFIYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

(risankizumab) -
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

heavy chain
VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLM

ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

SEQ ID NO: 75
DIQMTQSPSSLSASVGDRVTITCKASRDVAIAVAWYQQKPGKVPKLLIYWA

anti-IL23
STRHTGVPSRFSGSGSRTDFTLTISSLQPEDVADYFCHQYSSYPFTFGSGTKL

antibody
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

(risankizumab) -
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

light chain
KSFNRGEC

SEQ ID NO: 76
QVQLVQSGAEVKKPGASVKVSCKASGYIFITYWMTWVRQAPGQGLEWM

anti-IL23
GQIFPASGSADYNEKFEGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCAR

antibody
GGGGFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

(tildrakizumab) -
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

heavy chain
VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLM

ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 77
DIQMTQSPSSLSASVGDRVTITCRTSENIYSYLAWYQQKPGKAPKLLIYNAK

anti-IL23
TLAEGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQHHYGIPFTFGQGTKVE

antibody
IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS

(tildrakizumab) -
GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK

light chain
SFNRGEC

SEQ ID NO: 78
QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIGY

anti-IL6R
ISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLART

antibody
TAMDYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

(tocilizumab) -
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

heavy chain
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD

ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 79
DIQMTQSPSSLSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYTS

anti-IL6R
RLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPYTFGQGTKV

antibody
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

(tocilizumab) -
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

light chain
KSFNRGEC

SEQ ID NO: 80
DVQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMG

anti-LAP
YISYDGTNNYNPSLKNRISITRDTSKHQFFLKLNSVTTEDTATYYCARSFYN

antibody (7H4) -
NYFDFWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

heavy chain
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 81
DIQMTOSPSSLSASLGGKVTITCKASODIDKYIAWYQHKPGKGPRLLIHYTS

anti-LAP
TLQPGIPSRFSGSGSGRDYSFNISNLEPEDIATYYCLQYDNLRTFGGGTKLEI

antibody (7H4) -
KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG

light chain
NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS

FNRGEC

SEQ ID NO: 82
QVQLVQSGAEVKKPGASVKVSCKASGLTIEDYYMHWVRQAPGQGLEWM

anti-LIV-1
GWIDPENGDTEYGPKFQGRVTMTRDTSINTAYMELSRLRSDDTAVYYCAV

antibody
HNAHYGTWFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL

(ladiratuzumab) -
VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT

heavy chain
YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKD

TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST

YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY

TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS

DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

SEQ ID NO: 83
DVVMTQSPLSLPVTLGQPASISCRSSQSLLHSSGNTYLEWYQQRPGQSPRPL

anti-LIV-1
IYKISTRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFG

antibody
GGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV

(ladiratuzumab) -
DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG

light chain
LSSPVTKSFNRGEC

SEQ ID NO: 84
EVQLVQSGAEVKKPGSSVKVSCKASGFTFTDYYIHWVKQAPGQGLEWIGL

anti-LRRC15
VYPYIGGTNYNQKFKGKATLTVDTSTTTAYMEMSSLRSEDTAVYYCARGD

an (ABBV-
NKYDAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

085-
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

huAD208.4.1) -
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

heavy chain
MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

SEQ ID NO: 85
FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

anti-LRRC15
DIVLTQSPDSLAVSLGERATINCRASQSVSTSSYSYMHWYQQKPGQPPKLLI

an (ABBV-
KYASSLESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCEQSWEIRTFGGG

085-
TKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDN

huAD208.4.1) -
ALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS

light chain
PVTKSFNRGEC

SEQ ID NO: 86
EVQLVQSGAEVKKPGASVKVSCKASGYKFSSYWIEWVKQAPGQGLEWIG

anti-LRRC15
EILPGSDTTNYNEKFKDRATFTSDTSINTAYMELSRLRSDDTAVYYCARDR

antibody (ABBV-
GNYRAWFGYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

085-huM25) -
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

heavy chain
CNVIVHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

SEQ ID NO: 87
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGGAVKFLIYYTS

anti-LRRC15
RLHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYFCQQGEALPWTFGGGTKV

antibody (ABBV-
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

085-huM25) -
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

light chain
KSFNRGEA

SEQ ID NO: 88
QVQLQQSGAEVKKFGASVKVSCEASGYTFPSYVLHWVKQAPGQGLEWIG

anti-MUC1
YINPYNDGTQYNKKFKGKATLTRDTSINTAYMELSRLRSDDTAVYYCARG

antibody
FGGSYGFAYWGQGTLVIVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

(clivatuzumab) -
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

heavy chain
NVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPRESQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNEALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVNHEALHNHYTQKSLSLSPGK

SEQ ID NO: 89
DIQLTQSPSSLSASVGDRVTMTCSASSSVSSSYLYWYQQKPGKAPKLWIYS

anti-MUC1
TSNLASGVPARFSGSGSGTDFTLTISSLQPEDSASYFCHQWNRYPYTFGGGT

antibody
RLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA

(clivatuzumab) -
LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP

light chain
VTKSFNRGEC

SEQ ID NO: 90
EVQLQESGPGLVKPSDTLSLTCAVSGYSIASGYYWNWIRQPPGKGLEWMG

anti-OX40
YISYDGSNNYNPSLGNRITISRDTSKNQVSLKLSSVTAVDTAVYYCVKTLPY

antibody (ABBV-
YFDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

368-Hu3726) -
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

heavy chain
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 91
DIQMTQTPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIFYTS

anti-OX40
RLHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQGNTLPLTFGQGTKL

antibody (ABBV-
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

368-Hu3726) -
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

light chain
KSFNRGEC

EVQLVQSGAEVKKPGSSVKVSCKASGFNIKDTYMHWVRQAPGQGLEWIG

SEQ ID NO: 92
RIDPANGNTKYDPKFQGRATITADTSTNTAYMELSSLRSEDTAVYYCARGG

anti-OX40
PAWFVYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

antibody (ABBV-
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

368-Hu3739) -
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

heavy chain
TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 93
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTS

anti-OX40
RLRSGLPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQGNTLPWTFGGGTKV

antibody (ABBV-
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

368-Hu3739) -
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

light chain
KSFNRGEC

SEQ ID NO: 94
EVQLVESGGGLVQPGGSLRLSCAVSGFSLTSYGVHWVRQAPGKGLEWLG

anti-OX40
VIWSGGSTDYNAAFISRLTISKDNSKSTVYLQMNSLRAEDTAVYYCAREEF

antibody (ABBV-
DYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT

368-Hu3741) -
VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS

heavy chain
NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEV

TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTV

LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMT

KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 95
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWFQQKPGKAPKLLIYYTS

anti-OX40
RLHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQGYTLPPTFGGGTKV

antibody (ABBV-
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

368-Hu3741) -
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

light chain
KSFNRGEC

SEQ ID NO: 96
QVQLVQSGSELKKPGASVKVSCKASGYTFTDYSMHWVRQAPGQGLKWM

anti-OX40
GWINTETGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCANP

antibody
YYDYVSYYAMDYWGOGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

(GSK3174998) -
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

heavy chain
TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 97
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-OX40
SYLYTGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCOQHYSTPRTFGQGTKL

antibody
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

(GSK3174998) -
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

light chain
KSFNRGEC

SEQ ID NO: 98
EVQLVQSGAEVKKPGESLRISCKGSGYTFTTYWMHWVRQATGQGLEWMG

anti-PD1
NIYPGTGGSNFDEKFKNRVTITADKSTSTAYMELSSLRSEDTAVYYCTRWT

antibody
TGTGAYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

(spartalizumab) -
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNV

heavy chain
DHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTP

EVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVL

TVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE

MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

RLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG

SEQ ID NO: 99
EIVLTQSPATLSLSPGERATLSCKSSQSLLDSGNQKNFLTWYQQKPGQAPRL

anti-PD1
LTYWASTRESGVPSRFSGSGSGTDFTFTISSLEAEDAATYYCQNDYSYPYTF

antibody
GQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK

(spartalizumab) -
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ

light chain
GLSSPVTKSFNRGEC

SEQ ID NO: 100
QVQLVQSGVEVKKPGASVKVSCKASGYTFTNYYMYWVRQAPGQGLEWM

anti-PD1
GGINPSNGGTNFNEKFKNRVTLTTDSSTTTAYMELKSLQFDDTAVYYCARR

antibody
DYRFDMGFDYWGQGITVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVK

(pembrolizumab) -
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

heavy chain
CNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK

SEQ ID NO: 101
EIVLTQSPATLSLSPGERATLSCRASKGVSTSGYSYLHWYQQKPGQAPRLLI

anti-PD1
YLASYLESGVPARFSGSGSGTDFTLTISSLEPEDFAVYYCQHSRDLPLTFGG

antibody
GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD

(pembrolizumab) -
NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS

light chain
SPVTKSFNRGEC

SEQ ID NO: 102
EIQLVQSGAEVKKPGSSVKVSCKASGYTFTHYGMNWVRQAPGQGLEWVG

anti-PD1
WVNTYTGEPTYADDFKGRLTFTLDTSTSTAYMELSSLRSEDTAVYYCTRE

antibody (ABBV-
GEGLGFGDWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

181) - heavy chain
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLM

ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 103
DVVMTQSPLSLPVTPGEPASISCRSSQSIVHSHGDTYLEWYLQKPGQSPQLL

anti -PD1
IYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHIPVTFG

antibody (ABBV. -
QGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV

181) - light chain
DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG

LSSPVTKSFNRGEC

SEQ ID NO: 104
QVQLVESGGGVVQPGRSLRLDCKASGITFSNSGMHWVRQAPGKGLEWVA

anti-PD1
VIWYDGSKRYYADSVKGRFTISRDNSKNTLFLQMNSLRAEDTAVYYCATN

antibody
DDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV

(nivolumab) -
TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHK

heavy chain
PSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLH

QDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN

QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTV

DKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK

SEQ ID NO: 105
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDAS

anti-PD1
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQSSNWPRTFGQGTKV

antibody
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

(nivolumab) -
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

light chain
KSFNRGEC

SEQ ID NO: 106
EVTLRESGPALVKPTQTLTLTCTFSGFSLSTYGMGVGWIRQPPGKALEWLA

anti-PDGF
NIWWDDDKYYNPSLKNRLTISKDTSKNQVVLTMTNMDPVDTATYYCARIE

antibody (ab1) -
SSGPKYSFDYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

heavy chain
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 107
EIVLTOSPGTLSLSPGERATLSCRASSGSIWYSFVSWYOQKPGQAPRLLIYA

anti-PDGF
DDQRASGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQSYGINIDVVFGGGT

antibody (ab1) -
KVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA

light chain
LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP

VTKSFNRGEC

SEQ ID NO: 108
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

antibody
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

(atezolizumab) -
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

heavy chain
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 109
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-PDL1
SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTK

antibody
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

(atezolizumab) -
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

light chain
TKSFNRGEC

SEQ ID NO: 110
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYIMMWVRQAPGKGLEWVSSI

anti-PDL1
YPSGGITFYADTVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARIKLG

antibody
TVTTVDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

(avelumab) -
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

heavy chain
NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 111
QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIY

anti-PDL1
DVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTRVFGT

antibody
GTKVTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKA

(avelumab) - light
DGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGS

chain
TVEKTVAPTECS

SEQ ID NO: 112
EVQLVESGGGLVQPGGSLRLSCAASGFTFSRYWMSWVRQAPGKGLEWVA

anti-PDL1
NIKQDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARE

antibody
GGWFGELAFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL

(durvalumab) -
VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT

heavy chain
YICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKD

TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST

YRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVY

TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS

DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 113
EIVLTQSPGTLSLSPGERATLSCRASQRVSSSYLAWYQQKPGQAPRLLIYDA

anti-PDL1
SSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSLPWTFGQGTK

antibody
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

(durvalumab) -
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

light chain
TKSFNRGEC

SEQ ID NO: 114
EVQLVQSGAEVKKPGSSVKVSCKASGYTFTTYWMHWVRQAPGQGLEWIG

anti-PRLR
EIDPSDSYSNYNQKFKDRATLTVDKSTSTAYMELSSLRSEDTAVYYCARNG

antibody (ab1) -
GLGPAWFSYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

heavy chain
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVIVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPCVFLFPPKPKDTLM

ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 115
DIQMTQSPSSVSASVGDRVTITCKASQYVGTAVAWYQQKPGKSPKLLIYSA

anti-PRLR
SNRYTGVPSRFSDSGSGTDFTLTISSLQPEDFATYFCQQYSSYPWTFGGGTK

antibody (ab1) -
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

light chain
TKSFNRGEC

SEQ ID NO: 116
QLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHPGKGLEWIGYIY

anti-PSCA
YSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSGTAADTAVYYCARDHITMV

antibody (ab1) -
RGVPKGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

heavy chain
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 117
QLTQSPSSLSASVGDRVTITCRASQSISRHLNWYQQKPGKAPKFLIYVASSL

anti-PSCA
QSGVPSRFSGSGSGTDFTLTISSLQPEDFATYFCQQSYSIPRTFGQGTKVEIK

antibody (ab1) -
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

light chain
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGEC

SEQ ID NO: 118
QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYVMHWVRQAPGKGLEWVA

anti-PSMA
IIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAGG

antibody (ab2) -
YNWNYEYHYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAA

heavy chain
LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

SEQ ID NO: 119
DIQMTQSPSSLSASVGDRVTITCRASQGITNYLAWFQQKPGKAPKSLIYAAS

anti-PSMA
SLQSGVPSKFSGSGSGTDFSLTISSLQPEDFATYYCQQYNSYPITFGQGTRLE

antibody (ab2) -
IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS

light chain
GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK

SFNRGEC

SEQ ID NO: 120
QVQLVESGGGVVQPGRSLRLSCAASGFAFSRYGMHWVRQAPGKGLEWVA

anti-PSMA
VIWYDGSNKYYADSVKGRFTISRDNSKNTQYLQMNSLRAEDTAVYYCAR

antibody (ab1) -
GGDFLYYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAAL

heavy chain
GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

SEQ ID NO: 121
DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKTGKVPKFLIYEAS

anti-PSMA
TLQSGVPSRFSGGGSGTDFTLTISSLQPEDVATYYCQNYNSAPFTFGPGTKV

antibody (ab1) -
DIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

light chain
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGEC

SEQ ID NO: 122
QVQLVQSGPEVKKPGASVKVSCKASGYTFTDYAVHWVRQAPGKRLEWIG

anti-PTK7
VISTYNDYTYNNQDFKGRVTMTRDTSASTAYMELSRLRSEDTAVYYCARG

antibody
NSYFYALDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

(hSC6.24) - heavy
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

chain
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 123
EIVLTQSPATLSLSPGERATLSCRASESVDSYGKSFMHWYQQKPGQAPRLLI

anti-PTK7
YRASNLESGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQSNEDPWTFGG

antibody
GTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD

(hSC6.24) - light
NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS

chain
SPVTKSFNRGEC

SEQ ID NO: 124
EVQLVQSGAEVKKPGESLKISCKGSGYSFTSSWINWVRQMPGKGLEWMGR

anti-SEZ6
IYPGEGDTNYSGNFEGQVTISADKSISTAYLQWSSLKASDTAMYYCTRGLV

antibody
MDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV

(hSC17.200) -
TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP

heavy chain
SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 125
EIVLTQSPATLSLSPGERATLSCRASQSVDYNGISYMHWYQQKPGQAPRLLI

anti-SEZ6
YAASNVQSGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQSIEDPPTFGGG

antibody
TKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDN

(hSC17.200) -
ALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSS

light chain
PVTKSFNRGEC

SEQ ID NO: 126
EVQLVESGGGLVQPGGSLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIG

anti-SLAMF7
EINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDG

antibody
NYWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

(elotuzumab) -
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

heavy chain
VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 127
DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWA

anti-SLAMF7
STRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTK

antibody
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

(elotuzumab) -
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

light chain
TKSFNRGEC

SEQ ID NO: 128
EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYAMSWVRQAPGKGLEWVSS

anti-TF antibody
ISGSGDYTYYTDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSP

(tisotumab) -
WGYYLDSWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

heavy chain
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 129
DIQMTQSPPSLSASAGDRVTITCRASQGISSRLAWYQQKPEKAPKSLIYAAS

anti-TF antibody
SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYNSYPYTFGQGTKL

(tisotumab) - light
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

chain
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGEC

SEQ ID NO: 130
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMG

anti-TGFb
GIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGLW

antibody (XOMA-
EVRALPSVYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

089) - heavy chain
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 131
SYELTQPPSVSVAPGQTARITCGANDIGSKSVHWYQQKAGQAPVLVVSEDI

anti-TGFb
IRPSGIPERISGSNSGNTATLTISRVEAGDEADYYCQVWDRDSDQYVFGTGT

antibody (XOMA-
KVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADS

089) - light chain
SPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVE

KTVAPTECS

SEQ ID NO: 132
QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSNVISWVRQAPGQGLEWMG

anti-TGFb
GVIPIVDIANYAQRFKGRVTITADESTSTTYMELSSLRSEDTAVYYCASTLG

antibody
LVLDAMDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD

(fresolimumab) -
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTC

heavy chain
NVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK

SEQ ID NO: 133
ETVLTQSPGTLSLSPGERATLSCRASQSLGSSYLAWYQQKPGQAPRLLIYGA

anti-TGFb
SSRAPGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYADSPITFGQGTRL

antibody
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

(fresolimumab) -
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

light chain
KSFNRGEC

SEQ ID NO: 134
QLQVQESGPGLVKPSETLSLTCTVSGGSISNSYFSWGWIRQPPGKGLEWIGS

anti-TGFbRII
FYYGEKTYYNPSLKSRATISIDTSKSQFSLKLSSVTAADTAVYYCPRGPTMI

antibody
RGVIDSWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

(LY3022859) -
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

heavy chain
HKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAEGAPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPSSIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 135
EIVLTQSPATLSLSPGERATLSCRASQSVRSYLAWYQQKPGQAPRLLIYDAS

anti-TGFbRII
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKV

antibody
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

(LY3022859) -
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKFDVYACEVTHQGLSSPVT

light chain
KSFNRGEC

SEQ ID NO: 136
QVQLQESGPGLVKPSETLSLTCAVSGYSITSDYAWNWIRQPPGKGLEWIGY

anti-TIGIT
ISYSGSTSYNPSLRSRVTISRDTSKNQFFLKLSSVTAADTAVYYCARRQVGL

antibody
GFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

(etigilimab) -
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

heavy chain
KPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 137
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-TIGIT
SYRYTGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQHYSTPWTFGQGTK

antibody
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

(etigilimab) - light
QSGNSQESVTEQDSKDSTYSLSNTLTLSKADYEKHKVYACEVTHQGLSSPV

chain
TKSFNRGEC

SEQ ID NO: 138
EVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLG

anti-TIGIT
KTYYRFKWYSDYAVSVKGRITINPDTSKNQFSLQLNSVTPEDTAVFYCTRE

antibody
STTYDLLAGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

(tiragolumab) -
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

heavy chain
TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 139
DIVMTQSPDSLAVSLGERATINCKSSQTVLYSSNNKKYLAWYQQKPGQPPN

anti-TIGIT
LLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPFT

antibody
FGPGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQW

(tiragolumab) -
KVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH

light chain
QGLSSPVTKSFNRGEC

SEQ ID NO: 140
QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIY

anti-TIM3
DVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCSSYADSVVFGGG

antibody (M6903)
TKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKAD

- heavy chain
SSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTV

EKTVAPTECS

SEQ ID NO: 141
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA

anti-TIM3
ISVSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKAN

antibody (M6903)
WGFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

- light chain
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 142
EVQLVESGGGLVQPGGSLRLSCAASGYDFTHYGMNWVRQAPGKGLEWV

anti-VEGF
GWINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAK

antibody
YPYYYGTSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAAL

(ranibizumab) -
GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

heavy chain
GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHLCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

SEQ ID NO: 143
DIQLTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTSS

anti-VEGF
LHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKVE

antibody
IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS

(ranibizumab) -
GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK

light chain
SFNRGEC

SEQ ID NO: 144
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anti-VEGF
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

antibody
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

(bevacizumab) -
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

heavy chain
QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 145
EVQLVESGGGLVQPGGSLRLSCAASGFTFSNFPMAWVRQAPGKGLEWVAT

anti-VEGF
ISSSDGTTYYRDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARGY

antibody (ABT-
YNSPFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

165) - heavy chain
PEPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 146
DIQMTQSPSSLSASVGDRVTITCRASEDIYSNLAWYQQKPGKAPKLLIYDTN

anti-VEGF
NLADGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYNNYPPTFGQGTKL

antibody (ABT-
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

165) - light chain
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGEC

SEQ ID NO: 147
EVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSS

anti-VEGFR
ISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARVTD

antibody
AFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

(ramucirumab) -
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

heavy chain
KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 148
DIQMTQSPSSVSASIGDRVTITCRASQGIDNWLGWYQQKPGKAPKLLIYDA

anti-VEGFR
SNLDTGVPSRFSGSGSGTYFTLTISSLQAEDFAVYFCQQAKAFPPTFGGGTK

antibody
VDIKGTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

(ramucirumab) -
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

light chain
TKSFNRGEC

SEQ ID NO: 149
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMG

anti-VISTA
GIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARSSY

antibody
GWSYEFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

(onvatilimab) -
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

heavy chain
NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 150
DIQMTQSPSSLSASVGDRVTITCRASQSIDTRLNWYQQKPGKAPKLLIYSAS

anti-VISTA
SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSAYNPITFGQGTKVE

antibody
IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS

(onvatilimab) -
GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK

light chain
SFNRGEC

SEQ ID NO: 151
QVQLVQSGAEVKKPGASVKVSCKASGYIFTAYTMHWVRQAPGQGLEWM

anti-cMet
GWIKPNNGLANYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCAR

antibody
SEITTEFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

(telisotuzumab) -
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

heavy chain
VNHKPSNTKVDKRVEPKSCDCHCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

SEQ ID NO: 152
DIVMTQSPDSLAVSLGERATINCKSSESVDSYANSFLHWYQQKPGQPPKLLI

anti-cMet
YRASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQSKEDPLTFGG

antibody
GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD

(telisotuzumab) -
NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS

light chain
SPVTKSFNRGEC

SEQ ID NO: 153
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEYTLHWVRQAPGQRLEWM

anti-claudin
GGINPNNGDTIYNQKFKGRVTITRDTSASTAYMELSSLRSEDTAVYYCARR

antibody
AITVYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

(hSC27.1) - heavy
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

chain
CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 154
DIQMTQSPSSVSASVGDRVTITCKASEDIYNRLAWYQQKPGKAPKLLIYGA

anti-claudin
TSLETGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQYWSTPLTFGQGTK

antibody
LEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

(hSC27. 1) - light
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

chain
TKSFNRGEC

SEQ ID NO: 155
QVQLVQSGAEVKKPGASVKVSCQASGYRFSNFVIHWVRQAPGQRFEWMG

anti- gp120
WINPYNGNKEFSAKFQDRVTFTADTSANTAYMELRSLRSADTAVYYCARV

antibody (B12) -
GPYSWDDSPQDNYYMDVWGKGTTVIVSSASTKGPSVFPLAPSSKSTSGGT

heavy chain
AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR

EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ

PREPQVYTLPPSREEMTKNQVSLTCLVKGFYSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP

GK

SEQ ID NO: 156
EIVLTQSPGTLSLSPGERATFSCRSSHSIRSRRVAWYQHKPGQAPRLVIHGVS

anti-gp120
NRASGISDRFSGSGSGTDFTLTITRVEPEDFALYYCQVYGASSYTFGQGTKL

antibody (B12) -
ERKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

light chain
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGEC

SEQ ID NO: 157
EVQLVQSGAEVKKPGASVKVSCKASGDTFKRYYVHWVRQAPGQGLEWM

anti-mesothelin
GIINPSGVSTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAEV

antibody (ABBV-
RGSGFNYFGMDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL

428) - heavy chain
VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT

YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKD

TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST

YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY

TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS

DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 158
SYELTQPPSVSVSPGQTASITCSGDKLGDKYASWYQQKPGQSPVLVIYQDN

anti-mesothelin
RRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSDTYVFGTGTK

antibody (ABBV-
VTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSS

428) - light chain
PVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK

TVAPTECS

SEQ ID NO: 159
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYNMNWVRQAPGKGLEWVS

anti-nectin4
YISSSSSTIYYADSVKGRFTISRDNAKNSLSLQMNSLRDEDTAVYYCARAY

antibody
YYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

(enfortumab) -
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

heavy chain
NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 160
DIQMTQSPSSVSASVGDRVTITCRASQGISGWLAWYQQKPGKAPKFLIYAA

anti-nectin4
STLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPPTFGGGTKV

antibody
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

(enfortumab) -
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

light chain
KSFNRGEC

SEQ ID NO: 161
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGE

anti-uPAR
INHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARGRRFG

antibody (ab1) -
DFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

heavy chain
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 162
QPVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYDD

anti-uPAR
SDRPPGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHSPFGTG

antibody (ab1) -
TKVTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKAD

light chain
GSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGST

VEKTVAPTECS

SEQ ID NO: 163
QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLG

anti-uPAR
RTYYRSKWYNDYAVSVKSRIIINPDTSKNQFSLQLNSVTPEDTAVYYCARD

antibody (ab2) -
PGGPLDDSFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV

heavy chain
KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY

ICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 164
LDVVMTQSPLSLPVTPGEPASISCRSSQSLLRSNGYNYLDWYLQKPGQSPQ

anti-uPAR
LLIYLGSIRASGVPDRFSGSGSGTDFTLRISRVEAEDVGVYYCMQALQTPFT

antibody (ab2) -
FGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQW

light chain
KVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH

QGLSSPVTKSFNRGEC

SEQ ID NO: 165
IWNIHGKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLN

BTLA ECD (25-
GTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHS

150)
TTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 166
KESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVK

BTLA ECD (31-
LEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTTLYVT

134)

SEQ ID NO: 167
KESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVK

BTLA ECD (31-
LEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTTLYVT

150)
DVKSASERPSKDEMAS

SEQ ID NO: 168
KESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVK

BTLA ECD (31-
LEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTTLYVT

157)
DVKSASERPSKDEMASRPWLLYR

SEQ ID NO: 169
PGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMS

PD1 ECD
PSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTY

LCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 170
DSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFHVVWHRESPSGQTD

PD1 ECD (HAC-
TLAAFPEDRSQPGQDARFRVTQLPNGRDFHMSVVRARRNDSGTYVCGVIS

V)
LAPKIQIKESLRAELRVTER

SEQ ID NO: 171
PGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFHVVWHRES

PD1 ECD (HAC-
PSGQTDTLAAFPEDRSQPGQDARFRVTQLPNGRDFHMSVVRARRNDSGTY

V_extended)
VCGVISLAPKIQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 172
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10 ECD
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

(17-546)
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 173
EEEVQIIQPDKSVSVAAGESAILHCTITSLFPVGPIQWFRGAGPARVLIYNQR

SIRPa ECD
QGPFPRVTTISETTRRENMDFSISISNITPADAGTYYCIKFRKGSPDTEFKSGA

(FD6)
GTELSVRAKPS

SEQ ID NO: 174
EEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQ

SIRPa ECD (31-
KEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVE

150)
FKSGAGTELSVRAKPS

SEQ ID NO: 175
EEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQ

SIRPa ECD (31-
KEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVE

373)
FKSGAGTELSVRAKPSAPVVSGPAARATPQHTVSFTCESHGFSPRDITLKWF

KNGNELSDFQTNVDPVGESVSYSIHSTAKVVLTREDVHSQVICEVAHVTLQ

GDPLRGTANLSETIRVPPTLEVTQQPVRAENQVNVTCQVRKFYPQRLQLTW

LENGNVSRTETASTVTENKDGTYNWMSWLLVNVSAHRDDVKLTCQVEHD

GQPAVSKSHDLKVSAHPKEQGSNTAAENTGSNERNIY

SEQ ID NO: 176
EEELQIIQPDKSVLVAAGETATLRCTITSLFPVGPIQWFRGAGPGRVLIYNQR

SIRPa ECD
QGPFPRVTTVSDTTKRNNMDFSIRIGNITPADAGTYYCIKFRKGSPDDVEFK

(CV1)
SGAGTELSVRAKPS

SEQ ID NO: 177
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbR ECD
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

(TGFbRII)
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 178
IPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSIT

TGFbR ECD
SICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

(TGFbRII-1)
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 179
NGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKN

TGFbR ECD
DENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDEC

(huTGFbRII-
NDNIIFSEEYNTSNPDGLGPVESSPGHGLDTAAAGPEPGALCELSPVSASHP

huTGFbRIII-
VQALMESFTVLSGCASRGTTGLPQEVHVLNLRTAGQGPGQLQREVTLHLN

huTGFbRII)
PISSVHIHHKSVVFLLNSPHPLVWHLKTERLATGVSRLFLVSEGSVVQFSSA

NFSLTAETEERNFPHGNEHLLNWARKEYGAVTSFTELKIARNIYIKVGEDQ

VFPPKCNIGKNFLSLNYLAEYLQPKAAEGCVMSSQPQNEEVHIIELITPNSNP

YSAFQVDITIDIRPSQEDLEVVKNLILILKCKKSVNWVIKSFDVKGSLKIIAPN

SIGFGKESERSMTMTKSIRDDIPSTQGNLVKWALDNGYSPITSYTMAPVAN

RFHLRLENNAEEMGDEEVHTIPPELRILLDPTCKAQLCKFCDVRFSTCDNQ

KSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDA

ASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 180
NGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKN

TGFbR ECD
DENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDEC

(RER)
NDNIIFSEEYNTSNPDGLGPVESSPGHGLDTAAAGPEPSTRCELSPINASHPV

QALMESFTVLSGCASHGTTGLPREVHVLNLRSTDQGPGQRQREVTLHLNPI

ASVHTHHKPIVFLLNSPQPLVWRLKTERLAAGVPRLFLVSEGSVVQFPSGN

FSLTAETEERNFPQENEHLLRWAQKEYGAVTSFTELKIARNIYIKVGEDQVF

PPTCNIGKNFLSLNYLAEYLQPKAAEGCVLPSQPHEKEVHIIELITPSSNPYS

AFQVDIIVDIRPAQEDPEVVKNLVLILKSKKSVNWVIKSFDVKGNLKVIAPN

SIGFGKESERSMTMTKLVRDDIPSTQENLMKWALDAGYRPVTSYTMAPVA

NRFHLRLENNEEMRDEEVHTIPPELRILLDPDKLPQLCKFCDVRFSTCDNQK

SCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAA

SPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 181
SEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRT

TIM3 ECD
DERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDE

KFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINL

TQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 182
SEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRT

TIM3 ECD
DERDVNYWTSRYWLNGDFRKGDVSLTIENVILADSGIYCCRIQIPGIMNDE

(hypoglycosylated
KFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINL

TIM3 (T80I,
IQISTLANELRDSRLANDLRDSGATIRIG

T153I))

SEQ ID NO: 183
SEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRT

TIM3 ECD
DERDVNYWTSRYWLNGDFRKGDVSLTIENVILADSGIYCCRIQIPGIMNDE

(hypoglycosylated
KFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINL

TIM3 (T80I)
TQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 184
ASVGLPSVSLDLPRLSIQKDILTIKANTTLQITCRGQRDLDWLWPNNQSGSE

VEGFR ECD
QRVEVTECSDGLFCKTLTIPKVIGNDTGAYKCFYRETDLASVIYVYVQDYR

(VEGFR2)
SPFIASVSDQHGVVYITENKNKTVVIPCLGSISNLNVSLCARYPEKRFVPDG

NRISWDSKKGFTIPSYMISYAGMVFCEAKINDESYQSIMYIVVVVGYRIYDV

VLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDL

KTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKP

FVAFGSGMESLVEATVGERVRIPAKYLGYPPPEIKWYKNGIPLESNHTIKAG

HVLTIMEVSERDTGNYTVILTNPISKEKQSHVVSLVVYVPPQIGEKSLISPVD

SYQYGTTQTLTCTVYAIPPPHHIHWYWQLEEECANEPSQAVSVTNPYPCEE

WRSVEDFQGGNKIEVNKNQFALIEGKNKTVSTLVIQAANVSALYKCEAVN

KVGRGERVISFHVTRGPEITLQPDMQPTEQESVSLWCTADRSTFENLTWYK

LGPQPLPIHVGELPTPVCKNLDTLWKLNATMFSNSTNDILIMELKNASLQD

QGDYVCLAQDRKTKKRHCVVRQLTVLERVAPTITGNLENQTTSIGESIEVS

CTASGNPPPQIMWFKDNETLVEDSGIVLKDGNRNLTIRRVRKEDEGLYTCQ

ACSVLGCAKVEAFFIIEGAQEKTNLE

SEQ ID NO: 185
SKLKDPELSLKGTQHIMQAGQTLHLQCRGEAAHKWSLPEMVSKESERLSIT

VEGFR ECD
KSACGRNGKQFCSTLTLNTAQANHTGFYSCKYLAVPTSKKKETESAIYIFIS

(VEGFR1)
DTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKR

IIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVQISTP

RPVKLLRGHTLVLNCTAFIPLNTRVQMTWSYPDEKNKRASVRRRIDQSNS

HANIFYSVLTIDKMQNKDKGLYTCRVRSGPSFKSVNTSVHIYDKAFITVKH

RKQQVLETVAGKRSYRLSMKVKAFPSPEVVWLKDGLPATEKSARYLTRG

YSLIIKDVTEEDAGNYTILLSIKQSNVFKNLTATLIVNVKPQIYEKAVSSFPD

PALYPLGSRQILTCTAYGIPQPTIKWFWHPCNHNHSEARCDFCSNNEESFIL

DADSNMGNRIESITQRMAIIEGKNKMASTLVVADSRISGIYICIASNKVGTV

GRNISFYITDVPNGFHVNLEKMPTEGEDLKLSCTVNKFLYRDVTWILLRTV

NNRTMHYSISKQKMAITKEHSITLNLTIMNVSLQDSGTYACRARNVYTGEE

ILQKKEITIRDQEAPYLLRNLSDHTVAISSSTTLDCHANGVPEPQITWFKNNH

KIQQEPGIILGPGSSTLFIERVTEEDEGVYHCKATNQKGSVESSAYLTVQGTS

DKSNLE

SEQ ID NO: 186
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFR ECD
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

(aflibercept)
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK

SEQ ID NO: 187
EKATKRNDEECEVQLNIKRNSKHSAWTGELFKIECPVKYCVHRPNVTWCK

mBTLA ECD
HNGTIWVPLEVGPQLYTSWEENRSVPVFVLHFKPIHLSDNGSYSCSTNFNS

(30-176)
QVINSHSVTIHVRERTQNSSEHPLIISDIPDATNASGPSTMEKRPG

SEQ ID NO: 188
ACPWAVSGARASPGSAASPRLREGPELSPDDPAGLLDLRQGMFAQLVAQN

41BBL ECD (50-
VLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLEL

254)
RRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQ

GRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLPSP

RSE

SEQ ID NO: 189
QRTDSIPNSPDNVPLKGGNCSEDLLCILKRAPFKKSWAYLQVAKHLNKTKL

CD30L ECD (63-
SWNKDGILHGVRYQDGNLVIQFPGLYFIICQLQFLVQCPNNSVDLKLELLIN

234)
KHIKKQALVTVCESGMQTKHVYQNLSQFLLDYLQVNTTISVNVDTFQYIDT

STFPLENVLSIFLYSNSD

SEQ ID NO: 190
HRRLDKIEDERNLHEDFVFMKTIQRCNTGERSLSLLNCEEIKSQFEGFVKDI

CD40L ECD (47-
MLNKEETKKENSFEMQKGDQNPQIAAHVISEASSKTTSVLQWAEKGYYTM

261)
SNNLVTLENGKQLTVKRQGLYYIYAQVTFCSNREASSQAPFIASLCLKSPGR

FERILLRAANTHSSAKPCGQQSIHLGGVFELQPGASVFVNVTDPSQVSHGTG

FTSFGLLKL

SEQ ID NO: 191
GDQNPQIAAHVISEASSKTTSVLQWAEKGYYTMSNNLVTLENGKQLTVKR

CD40L ECD
QGLYYIYAQVTFCSNREASSQAPFIASLCLKSPGRFERILLRAANTHSSAKPC

(116-261)
GQQSIHLGGVFELQPGASVFVNVTDPSQVSHGTGFTSFGLLKL

SEQ ID NO: 192
QRFAQAQQQLPLESLGWDVAELQLNHTGPQQDPRLYWQGGPALGRSFLH

CD70 ECD (39-
GPELDKGQLRIHRDGIYMVHIQVTLAICSSTTASRHHPTTLAVGICSPASRSI

193)
SLLRLSFHQGCTIASQRLTPLARGDTLCTNLTGTLLPSRNTDETFFGVQWVR

P

SEQ ID NO: 193
QLETAKEPCMAKFGPLPSKWQMASSEPPCVNKVSDWKLEILQNGLYLIYG

GITRL ECD (72-
QVAPNANYNDVAPFEVRLYKNKDMIQTLTNKSKIQNVGGTYELHVGDTID

199)
LIFNSEHQVLKNNTYWGIILLANPQFIS

SEQ ID NO: 194
DTQEKEVRAMVGSDVELSCACPEGSRFDLNDVYVYWQTSESKTVVTYHIP

ICOSL ECD (19-
QNSSLENVDSRYRNRALMSPAGMLRGDFSLRLFNVTPQDEQKFHCLVLSQ

258)
SLGFQEVLSVEVTLHVAANFSVPVVSAPHSPSQDELTFTCTSINGYPRPNVY

WINKTDNSLLDQALQNDTVFLNMRGLYDVVSVLRIARTPSVNIGCCIENVL

LQQNLTVGSQTGNDIGERDKITENPVSTGEKNAATWS

SEQ ID NO: 195
IWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSG

IL12 ECD (p40-
KTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEP

p35)
KNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQGVTCGAAT

LSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHKLKYENYT

SSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQV

QGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEWASVPCS

GGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKAR

QTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITNGSC

LASRKTSFMNIALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNML

AVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAVTIDRV

MSYLNAS

SEQ ID NO: 196
NWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVISL

IL15 ECD (49-
ESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVH

162)
IVQMFINTS

SEQ ID NO: 197
LQLHWRLGEMVTRLPDGPAGSWEQLIQERRSHEVNPAAHLTGANSSLTGS

(LIGHT ECD (59-
GGPLLWETQLGLAFLRGLSYHDGALVVTKAGYYYIYSKVQLGGVGCPLGL

240)
ASTITHGLYKRTPRYPEELELLVSQQSPCGRATSSSRVWWDSSFLGGVVHL

EAGEKVVVRVLDERLVRLRDGTRSYFGAFMV

SEQ ID NO: 198
DGPAGSWEQLIQERRSHEVNPAAHLTGANSSLTGSGGPLLWETQLGLAFLR

LIGHT ECD (74-
GLSYHDGALVVTKAGYYYIYSKVQLGGVGCPLGLASTITHGLYKRTPRYP

240)
EELELLVSQQSPCGRATSSSRVWWDSSFLGGVVHLEAGEKVVVRVLDERL

VRLRDGTRSYFGAFMV

SEQ ID NO: 199
QVSHRYPRIQSIKVQFTEYKKEKGFILTSQKEDEIMKVQNNSVIINCDGFYLI

OX40L ECD (51-
SLKGYFSQEVNISLHYQKDEEPLFQLKKVRSVNSLMVASLTYKDKVYLNV

183)
TTDNTSLDDFHVNGGELILIHQNPGEFCVL

SEQ ID NO: 200
GGGGSGGGGSGGGGS

flexible linker -

(GGGGS)3

SEQ ID NO: 201
GGGGSGGGGSGGGGSGGGGS

flexible linker -

(GGGGS)4

SEQ ID NO: 202
GSAGSAAGSGEF

flexible linker -

waldo 1999

SEQ ID NO: 203
KESGSVSSEQLAQFRSLD

flexible linker -

bird1988-1

SEQ ID NO: 204
EGKSSGSGSESKST

flexible linker -

bird1988-2

SEQ ID NO: 205
EAAAKEAAAKEAAAK

rigid linker -

(EAAAK)3

SEQ ID NO: 206
AEAAAKEAAAKEAAAKA

rigid linker -

A(EAAAK)3 A

SEQ ID NO: 207
APAPAPAPAPAPAP

rigid linker -

(AP)7

SEQ ID NO: 208
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH

HC constant
TFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSC

region - IgG1
DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK

CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGF

YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV

FSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 209
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH

HC constant
TFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSC

region -
DKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

IgG1_L234A_L23
VKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK

5A
CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGF

YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV

FSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 210
ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHT

HC constant
FPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYG

region - IgG4
PPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFN

WYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVS

NKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSD

IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV

MHEALHNHYTQKSLSLSLGK

SEQ ID NO: 211
ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHT

HC constant
FPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYG

region -
PPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFN

IgG4_S228P
WYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVS

NKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSD

IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQQGNVFSCSV

MHEALHNHYTQKSLSLSGK

SEQ ID NO: 212
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

LC constant
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

region - kappa
NRGEC

SEQ ID NO: 213
QPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAG

LC constant
VETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPT

region - lambda
ECS

SEQ ID NO: 214
DIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPPKLLI

anti-CD3/CD19
YDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFG

BiTE
GGTKLEIKGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGY

(blinatumomab)
AFSSYWMNWVKQRPGQGLEWIGQIWPGDGDTNYNGKFKGKATLTADESS

STAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYWGQGTTVTVSSG

GGGSDIKLQQSGAELARPGASVKMSCKTSGYTFTRYTMHWVKQRPGQGL

EWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYC

ARYYDDHYCLDYWGQGTTLTVSSVEGGSGGSGGSGGSGGVDDIQLTQSPA

IMSASPGEKVTMTCRASSSVSYMNWYQQKSGTSPKRWIYDTSKVASGVPY

RFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELKHHHH

HH

SEQ ID NO: 215
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVA

anti-CD3/PSMA
IISDGGYYTYYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFP

BiTE
LLRHGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASV

(pasotuxizumab)
GDRVTITCKASQNVDTNVAWYQQKPGQAPKSLIYSASYRYSDVPSRFSGSA

SGTDFTLTISSVQSEDFATYYCQQYDSYPYTFGGGTKLEIKSGGGGSEVQLV

ESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSK

YNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGN

FGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARF

SGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLHHHH

HH

SEQ ID NO: 216
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

anti-
GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR

CEACAM5/CD3
WDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

CrossMab
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

(cibisatamab) -
TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKP

HC1
KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREP

QVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 217
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

anti-
GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR

CEACAM5/CD3
WDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

CrossMab
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

(cibisatamab) -
TYICNVNHKPSNTKVDKKVEPKSCDGGGGSGGGGSEVQLLESGGGLVQPG

HC2
GSLRLSCAASGFTFSTYAMNWVRQAPGKGLEWVSRIRSKYNNYATYYADS

VKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCVRHGNFGNSYVSWFAY

WGQGTLVTVSSASVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ

WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT

HQGLSSPVTKSFNRGECDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPC

RDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO: 218
DIQMTQSPSSLSASVGDRVTITCKASAAVGTYVAWYQQKPGKAPKLLIYSA

anti-
SYRKRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQYYTYPLFTFGQGT

CEACAM5/CD3
KLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA

CrossMab
LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP

(cibisatamab) -
VTKSFNRGEC

LC1

SEQ ID NO: 219
QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTTSNYANWVQEKPGQAFRGLIG

anti-
GTNKRAPGTPARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNLWVFG

CEACAM5/CD3
GGTKLTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW

CrossMab
NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK

(cibisatamab) -
VDKKVEPKSC

LC2

SEQ ID NO: 220
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to BTLA
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFYAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

HCTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKL

NGTTCVKLEDRQTSWKEEKNISFFILHEEPVLPNDNGSYRCSANFQSNLIES

HSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 221
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES

anti-EGFR LC
ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK

fused to PD1 ECD
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNA

TFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLP

NGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVP

TAHPSPSPRPAGQFQTLV

SEQ ID NO: 222
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES

anti-EGFR LC
ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK

fused to
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

SIGLEC10 ECD
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYP

RQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGD

PAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQK

PDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFS

VLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDN

TPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHP

WGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVM

VSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSP

SQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSC

SWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWAN

SSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 223
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES

anti-EGFR LC
ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK

fused to SIRPa
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

ECD
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLI

PVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITP

ADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 224
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES

anti-EGFR LC
ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK

fused to TIM3
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

ECD
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPV

CWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENV

TLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRML

TTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 225
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR HC
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to PD1 ECD
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVL

NWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRAR

RNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQF

QTLV

SEQ ID NO: 226
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES

anti-EGFR LC
ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK

fused to BTLA
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

ECD
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVK

YCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHEEPVLPNDNGS

YRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 227
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR HC
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

SIGLEC10 ECD
EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGY

WFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQ

MQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQP

VTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNT

DLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVP

YLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGV

KAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENL

GNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPR

VQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCS

SQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSG

LRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 228
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR HC
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to SIRPa
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPG

RELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRK

GSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 229
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR HC
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to TGFbR
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQK

SCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAA

SPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 230
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR HC
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to TIM3
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECG

NVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIP

GIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLG

SLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 231
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR HC
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to VEGFR
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPL

DTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQT

NTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKL

VNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVR

VHEK

SEQ ID NO: 232
QVQLQESGPGLVKPSQTLSLTCTVSGYSISSDFAWNWIRQPPGKGLEWMG

anti-EGFRvIII
YISYSGNTRYQPSLKSRITISRDTSKNQFFLKLNSVTAADTATYYCVTAGRG

HC fused to
FPYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV

BTLA ECD
TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP

SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLNGT

TCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTT

LYVTDVKSASERPSKDEMAS

SEQ ID NO: 233
DIQMTQSPSSMSVSVGDRVTITCHSSQDINSNIGWLQQKPGKSFKGLIYHGT

anti-EGFRvIII
NLDDGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCVQYAQFPWTFGGGTK

LC fused to PD1
LEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTE

GDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRV

TQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERR

AEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 234
DIQMTQSPSSMSVSVGDRVTITCHSSQDINSNIGWLQQKPGKSFKGLIYHGT

anti-EGFRvIII
NLDDGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCVQYAQFPWTFGGGTK

LC fused to
LEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

SIGLEC10 ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCS

FSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQL

TGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTAL

TQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTT

SHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISIS

RDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLS

SSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 235
DIQMTQSPSSMSVSVGDRVTITCHSSQDINSNIGWLQQKPGKSFKGLIYHGT

anti-EGFRvIII
NLDDGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCVQYAQFPWTFGGGTK

LC fused to
LEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

SIRPa ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCT

ATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRI

GNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 236
DIQMTQSPSSMSVSVGDRVTITCHSSQDINSNIGWLQQKPGKSFKGLIYHGT

anti-EGFRvIII
NLDDGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCVQYAQFPWTFGGGTK

LC fused to TIM3
LEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGN

LVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSL

TIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAF

PRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRI

G

SEQ ID NO: 237
QVQLQESGPGLVKPSQTLSLTCTVSGYSISSDFAWNWIRQPPGKGLEWMG

anti-EGFRvIII
YISYSGNTRYQPSLKSRITISRDTSKNQFFLKLNSVTAADTATYYCVTAGRG

HC fused to PD1
FPYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV

ECD
TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP

SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNW

YRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRND

SGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTL

V

SEQ ID NO: 238
DIQMTQSPSSMSVSVGDRVTITCHSSQDINSNIGWLQQKPGKSFKGLIYHGT

anti-EGFRAII
NLDDGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCVQYAQFPWTFGGGTK

LC fused to
LEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

BTLA ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELE

CPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPN

DNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 239
QVQLQESGPGLVKPSQTLSLTCTVSGYSISSDFAWNWIRQPPGKGLEWMG

anti-EGFRvIII
YISYSGNTRYQPSLKSRITISRDTSKNQFFLKLNSVTAADTATYYCVTAGRG

HC fused to
FPYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV

SIGLEC10 ECD
TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP

SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFK

AVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQD

ESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVI

CVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTC

HVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEA

QKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAG

DSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGT

SLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVE

HEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASP

APSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRC

EAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 240
QVQLQESGPGLVKPSQTLSLTCTVSGYSISSDFAWNWIRQPPGKGLEWMG

anti-EGFRvIII
YISYSGNTRYQPSLKSRITISRDTSKNQFFLKLNSVTAADTATYYCVTAGRG

HC fused to
FPYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV

SIRPa ECD
TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP

SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGREL

IYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPD

DVEFKSGAGTELSVRAKPS

SEQ ID NO: 241
QVQLQESGPGLVKPSQTLSLTCTVSGYSISSDFAWNWIRQPPGKGLEWMG

anti-EGFRvIII
YISYSGNTRYQPSLKSRITISRDTSKNQFFLKLNSVTAADTATYYCVTAGRG

HC fused to
FPYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV

TGFbRECD
TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP

SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCM

SNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPK

CIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 242
QVQLQESGPGLVKPSQTLSLTCTVSGYSISSDFAWNWIRQPPGKGLEWMG

anti-EGFRvIII
YISYSGNTRYQPSLKSRITISRDTSKNQFFLKLNSVTAADTATYYCVTAGRG

HC fused to TIM3
FPYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV

ECD
TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP

SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNV

VLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGI

MNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSL

PDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 243
QVQLQESGPGLVKPSQTLSLTCTVSGYSISSDFAWNWIRQPPGKGLEWMG

anti-EGFRAII
YISYSGNTRYQPSLKSRITISRDTSKNQFFLKLNSVTAADTATYYCVTAGRG

HC fused to
FPYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV

VEGFR ECD
TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP

SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLI

PDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIID

VVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRD

LKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK

SEQ ID NO: 244
EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVAR

anti-HER2 HC
IYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWG

fused to BTLA
GDGFYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVT

WCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQS

NLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 245
DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSA

anti-HER2 LC
SFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKV

fused to PD1 ECD
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEG

DNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVT

QLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRA

EVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 246
DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSA

anti-HER2 LC
SFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKV

fused to
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

SIGLEC10 ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSF

SYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQL

TGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTAL

TQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTT

SHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISIS

RDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLS

SSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 247
DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSA

anti-HER2 LC
SFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKV

fused to SIRPa
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTA

TSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIG

NITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 248
DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSA

anti-HER2 LC
SFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKV

fused to TIM3
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNL

VPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTI

ENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFP

RMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRI

G

SEQ ID NO: 249
EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVAR

anti-HER2 HC
IYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWG

fused to PD1 ECD
GDGFYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTS

ESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSV

VRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRP

AGQFQTLV

SEQ ID NO: 250
DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSA

anti-HER2 LC
SFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKV

fused to BTLA
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELEC

PVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPND

NGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 251
EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVAR

anti-HER2 HC
IYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWG

fused to
GDGFYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

SIGLEC10 ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTP

AYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVI

RDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLE

PGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQ

DHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQ

GNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGL

ELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTV

LENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGV

LELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGL

HCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHG

GLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 252
EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVAR

anti-HER2 HC
IYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWG

fused to SIRPa
GDGFYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRG

AGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCV

KFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 253
EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVAR

anti-HER2 HC
IYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWG

fused to TGFbR
GDGFYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTC

DNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFIL

EDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 254
EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVAR

anti-HER2 HC
IYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWG

fused to TIM3
GDGFYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACP

VFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYC

CRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAE

TQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 255
EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVAR

anti-HER2 HC
IYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWG

fused to VEGFR
GDGFYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLK

KFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTH

RQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQH

KKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNS

TFVRVHEK

SEQ ID NO: 256
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYNMNWVRQAPGKGLEWVS

anti-nectin4 HC
YISSSSSTIYYADSVKGRFTISRDNAKNSLSLQMNSLRDEDTAVYYCARAY

fused to BTLA
YYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

ECD
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCK

LNGTTCVKLEDRQTSWKEEKNISFFILHEEPVLPNDNGSYRCSANFQSNLIE

SHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 257
DIQMTQSPSSVSASVGDRVTITCRASQGISGWLAWYQQKPGKAPKFLIYAA

anti-nectin4 LC
STLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPPTFGGGTKV

fused to PD1 ECD
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEG

DNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVT

QLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRA

EVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 258
DIQMTQSPSSVSASVGDRVTITCRASQGISGWLAWYQQKPGKAPKFLIYAA

anti-nectin4 LC
STLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPPTFGGGTKV

fused to
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

SIGLEC10 ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSF

SYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQL

TGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTAL

TQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTT

SHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISIS

RDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLS

SSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 259
DIQMTQSPSSVSASVGDRVTITCRASQGISGWLAWYQQKPGKAPKFLIYAA

anti-nectin4 LC
STLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPPTFGGGTKV

fused to SIRPa
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTA

TSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIG

NITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 260
DIQMTQSPSSVSASVGDRVTITCRASQGISGWLAWYQQKPGKAPKFLIYAA

anti-nectin4 LC
STLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPPTFGGGTKV

fused to TIM3
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNL

VPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTI

ENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFP

RMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRI

G

SEQ ID NO: 261
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYNMNWVRQAPGKGLEWVS

anti-nectin4 HC
YISSSSSTIYYADSVKGRFTISRDNAKNSLSLQMNSLRDEDTAVYYCARAY

fused to PD1 ECD
YYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFV

LNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRA

RRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQ

FQTLV

SEQ ID NO: 262
DIQMTQSPSSVSASVGDRVTITCRASQGISGWLAWYQQKPGKAPKFLIYAA

anti-nectin4 LC
STLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPPTFGGGTKV

fused to BTLA
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELEC

PVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPND

NGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 263
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYNMNWVRQAPGKGLEWVS

anti-nectin4 HC
YISSSSSTIYYADSVKGRFTISRDNAKNSLSLQMNSLRDEDTAVYYCARAY

fused to
YYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

SIGLEC10 ECD
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYG

YWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDA

QMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQ

PVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHN

TDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNV

PYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPG

VKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLEN

LGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELP

RVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSC

SSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSS

GLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 264
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYNMNWVRQAPGKGLEWVS

anti-nectin4 HC
YISSSSSTIYYADSVKGRFTISRDNAKNSLSLQMNSLRDEDTAVYYCARAY

fused to SIRPa
YYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

ECD
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGP

GRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFR

KGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 265
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYNMNWVRQAPGKGLEWVS

anti-nectin4 HC
YISSSSSTIYYADSVKGRFTISRDNAKNSLSLQMNSLRDEDTAVYYCARAY

fused to TGFbR
YYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

ECD
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQ

KSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDA

ASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 266
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYNMNWVRQAPGKGLEWVS

anti-nectin4 HC
YISSSSSTIYYADSVKGRFTISRDNAKNSLSLQMNSLRDEDTAVYYCARAY

fused to TIM3
YYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

ECD
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFEC

GNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQI

PGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTL

GSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 267
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYNMNWVRQAPGKGLEWVS

anti-nectin4 HC
YISSSSSTIYYADSVKGRFTISRDNAKNSLSLQMNSLRDEDTAVYYCARAY

fused to VEGFR
YYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

ECD
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFP

LDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQT

NTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKL

VNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVR

VHEK

SEQ ID NO: 268
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGE

anti-uPAR HC
INHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARGRRFG

fused to BTLA
DFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

ECD
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLN

GTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHS

TTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 269
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGE

anti-uPAR HC
INHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARGRRFG

fused to PD1 ECD
DFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLN

WYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARR

NDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQ

TLV

SEQ ID NO: 270
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGE

anti-uPAR HC
INHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARGRRFG

fused to
DFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

SIGLEC10 ECD
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYW

FKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQM

QDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVT

VICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDL

TCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYL

EAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVK

AGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLG

NGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRV

QVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSS

QASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGL

RLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 271
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGE

anti-uPA RHC
INHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARGRRFG

fused to SIRPa
DFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

ECD
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGR

ELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGS

PDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 272
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGE

anti-uPAR HC
INHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARGRRFG

fused to TGFbR
DFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

ECD
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKS

CMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAAS

PKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 273
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGE

anti-uPAR HC
INHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARGRRFG

fused to TIM3
DFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

ECD
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGN

VVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPG

IMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGS

LPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 274
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGE

anti-uPAR HC
INHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARGRRFG

fused to VEGFR
DFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

ECD
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDT

LIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTI

IDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVN

RDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVH

EK

SEQ ID NO: 275
QVQLVESGGGVVQPGRSLRLSCAASGFAFSRYGMHWVRQAPGKGLEWVA

anti-PSMA HC
VIWYDGSNKYYADSVKGRFTISRDNSKNTQYLQMNSLRAEDTAVYYCAR

fused to BTLA
GGDFLYYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAAL

ECD
GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

KGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCAN

RPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCS

ANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 276
QVQLVESGGGVVQPGRSLRLSCAASGFAFSRYGMHWVRQAPGKGLEWVA

anti-PSMA HC
VIWYDGSNKYYADSVKGRFTISRDNSKNTQYLQMNSLRAEDTAVYYCAR

fused to PD1 ECD
GGDFLYYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAAL

GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

KGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTC

SFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRD

FHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHP

SPSPRPAGQFQTLV

SEQ ID NO: 277
QVQLVESGGGVVQPGRSLRLSCAASGFAFSRYGMHWVRQAPGKGLEWVA

anti-PSMA HC
VIWYDGSNKYYADSVKGRFTISRDNSKNTQYLQMNSLRAEDTAVYYCAR

fused to
GGDFLYYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAAL

SIGLEC10 ECD
GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

KGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDW

TGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKG

NCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVY

IPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSF

TPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPAL

EPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGP

RPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQ

ANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQP

SDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSW

EAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSS

LSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 278
QVQLVESGGGVVQPGRSLRLSCAASGFAFSRYGMHWVRQAPGKGLEWVA

anti-PSMA HC
VIWYDGSNKYYADSVKGRFTISRDNSKNTQYLQMNSLRAEDTAVYYCAR

fused to SIRPa
GGDFLYYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAAL

ECD
GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

KGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPI

QWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAG

TYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 279
QVQLVESGGGVVQPGRSLRLSCAASGFAFSRYGMHWVRQAPGKGLEWVA

anti-PSMA HC
VIWYDGSNKYYADSVKGRFTISRDNSKNTQYLQMNSLRAEDTAVYYCAR

fused to TGFbR
GGDFLYYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAAL

ECD
GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

KGGGGSGGGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDV

RFSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLP

YHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 280
QVQLVESGGGVVQPGRSLRLSCAASGFAFSRYGMHWVRQAPGKGLEWVA

anti-PSMA HC
VIWYDGSNKYYADSVKGRFTISRDNSKNTQYLQMNSLRAEDTAVYYCAR

fused to TIM3
GGDFLYYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAAL

ECD
GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

KGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWG

KGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLA

DSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTR

GHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 281
QVQLVESGGGVVQPGRSLRLSCAASGFAFSRYGMHWVRQAPGKGLEWVA

anti-PSMA HC
VIWYDGSNKYYADSVKGRFTISRDNSKNTQYLQMNSLRAEDTAVYYCAR

fused to VEGFR
GGDFLYYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAAL

ECD
GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

KGGGGSGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNI

TVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKT

NYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPS

SKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLM

TKKNSTFVRVHEK

SEQ ID NO: 282
EVQLVESGGGVVQPGRSLRLSCSASGFDFTTYWMSWVRQAPGKGLEWIGE

anti-CEACAM5
IHPDSSTINYAPSLKDRFTISRDNAKNTLFLQMDSLRPEDTGVYFCASLYFGF

HC fused to
PWFAYWGQGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

BTLAECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLN

GTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHS

TTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 283
EVQLVESGGGVVQPGRSLRLSCSASGFDFTTYWMSWVRQAPGKGLEWIGE

anti-CEACAM5
IHPDSSTINYAPSLKDRFTISRDNAKNTLFLQMDSLRPEDTGVYFCASLYFGF

HC fused to PD1
PWFAYWGQGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLN

WYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARR

NDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQ

TLV

SEQ ID NO: 284
EVQLVESGGGVVQPGRSLRLSCSASGFDFTTYWMSWVRQAPGKGLEWIGE

anti-CEACAM5
IHPDSSTINYAPSLKDRFTISRDNAKNTLFLQMDSLRPEDTGVYFCASLYFGF

HC fused to
PWFAYWGQGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

SIGLEC10 ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYW

FKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQM

QDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVT

VICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDL

TCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYL

EAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVK

AGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLG

NGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRV

QVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSS

QASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGL

RLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 285
EVQLVESGGGVVQPGRSLRLSCSASGFDFTTYWMSWVRQAPGKGLEWIGE

anti-CEACAM5
IHPDSSTINYAPSLKDRFTISRDNAKNTLFLQMDSLRPEDTGVYFCASLYFGF

HC fused to
PWFAYWGQGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

SIRPa ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGR

ELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGS

PDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 286
EVQLVESGGGVVQPGRSLRLSCSASGFDFTTYWMSWVRQAPGKGLEWIGE

anti-CEACAM5
IHPDSSTINYAPSLKDRFTISRDNAKNTLFLQMDSLRPEDTGVYFCASLYFGF

HC fused to
PWFAYWGQGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

TGFbR ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKS

CMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAAS

PKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 287
EVQLVESGGGVVQPGRSLRLSCSASGFDFTTYWMSWVRQAPGKGLEWIGE

anti-CEACAM5
IHPDSSTINYAPSLKDRFTISRDNAKNTLFLQMDSLRPEDTGVYFCASLYFGF

HC fused to TIM3
PWFAYWGQGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGN

VVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPG

IMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGS

LPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 288
EVQLVESGGGVVQPGRSLRLSCSASGFDFTTYWMSWVRQAPGKGLEWIGE

anti-CEACAM5
IHPDSSTINYAPSLKDRFTISRDNAKNTLFLQMDSLRPEDTGVYFCASLYFGF

HC fused to
PWFAYWGQGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

VEGFR ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDT

LIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTI

IDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVN

RDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVH

EK

SEQ ID NO: 289
EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSA

anti-CD38 HC
ISGSGGGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKI

fused to BTLA
LWFGEPVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVT

WCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQS

NLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 290
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDAS

anti-CD38 LC
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKV

fused to PD1 ECD
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEG

DNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVT

QLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRA

EVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 291
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDAS

anti-CD38 LC
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKV

fused to
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

SIGLEC10 ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSF

SYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQL

TGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTAL

TQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTT

SHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISIS

RDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLS

SSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 292
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDAS

anti- CD38 LC
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKV

fused to SIRPa
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTA

TSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIG

NITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 293
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDAS

anti-CD38 LC
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKV

fused to TIM3
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNL

VPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTI

ENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFP

RMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRI

G

SEQ ID NO: 294
EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSA

anti-CD38 HC
ISGSGGGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKI

fused to PD1 ECD
LWFGEPVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTS

ESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSV

VRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRP

AGQFQTLV

SEQ ID NO: 295
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDAS

anti- CD38 LC
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKV

fused to BTLA
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELEC

PVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPND

NGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 296
EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSA

anti-CD38 HC
ISGSGGGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKI

fused to
LWFGEPVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

SIGLEC10 ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTP

AYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVI

RDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLE

PGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQ

DHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQ

GNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGL

ELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTV

LENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGV

LELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGL

HCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHG

GLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 297
EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSA

anti-CD38 HC
ISGSGGGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKI

fused to SIRPa
LWFGEPVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRG

AGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCV

KFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 298
EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSA

anti-CD38 HC
ISGSGGGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKI

fused to TGFbR
LWFGEPVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTC

DNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFIL

EDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 299
EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSA

anti-CD38 HC
ISGSGGGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKI

fused to TIM3
LWFGEPVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACP

VFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYC

CRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAE

TQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 300
EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSA

anti-CD38 HC
ISGSGGGTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKI

fused to VEGFR
LWFGEPVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK

ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLK

KFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTH

RQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQH

KKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNS

TFVRVHEK

SEQ ID NO: 301
EVQLVESGGGLVQPGGSLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIG

anti-SLAMF7
EINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDG

HC fused to
NYWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

BTLA ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWC

KLNGTTCVKLEDRQTSWKEEKNISFFILHEEPVLPNDNGSYRCSANFQSNLI

ESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 302
DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWA

anti-SLAMF7 LC
STRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTK

fused to PD1 ECD
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTE

GDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRV

TQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERR

AEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 303
DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWA

anti-SLAMF7 LC
STRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTK

fused to
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

SIGLEC10 ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCS

FSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQL

TGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTAL

TQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTT

SHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISIS

RDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLS

SSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 304
DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWA

anti-SLAMF7 LC
STRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTK

fused to SIRPa
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCT

ATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRI

GNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 305
DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWA

anti-SLAMF7 LC
STRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTK

fused to TIM3
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGN

LVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSL

TIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAF

PRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRI

G

SEQ ID NO: 306
EVQLVESGGGLVQPGGSLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIG

anti-SLAMF7
EINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDG

HC fused to PD1
NYWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESF

VLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVR

ARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAG

QFQTLV

SEQ ID NO: 307
DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWA

anti-SLAMF7 LC
STRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTK

fused to BTLA
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELE

CPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPN

DNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 308
EVQLVESGGGLVQPGGSLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIG

anti-SLAMF7
EINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDG

HC fused to
NYWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

SIGLEC10 ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAY

GYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRD

AQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPG

QPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDH

NTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGN

VPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELP

GVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLE

NLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLE

LPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHC

SCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLS

SGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 309
EVQLVESGGGLVQPGGSLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIG

anti-SLAMF7
EINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDG

HC fused to
NYWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

SIRPa EC
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGA

GPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKF

RKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 310
EVQLVESGGGLVQPGGSLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIG

anti-SLAMF7
EINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDG

HC fused to
NYWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

TGFbR EC
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDN

QKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILED

AASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 311
EVQLVESGGGLVQPGGSLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIG

anti-SLAMF7
EINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDG

HC fused to TIM3
NYWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVF

ECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCR

IQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLFERGHGPAETQ

TLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 312
EVQLVESGGGLVQPGGSLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIG

anti-SLAMF7
EINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDG

HC fused to
NYWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

VEGFR ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKF

PLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQ

TNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKK

LVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFV

RVHEK

SEQ ID NO: 313
QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIGY

anti-IL6R HC
ISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLART

fused to BTLA
TAMDYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD

ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLN

GTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHS

TTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 314
DIQMTQSPSSLSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYTS

anti-IL6R LC
RLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPYTFGQGTKV

fused to PD1 ECD
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEG

DNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVT

QLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRA

EVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 315
DIQMTQSPSSLSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYTS

anti-IL6R LC
RLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPYTFGQGTKV

fused to
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

SIGLEC10 ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSF

SYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQL

TGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTAL

TQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTT

SHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISIS

RDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLS

SSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 316
DIQMTQSPSSLSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYTS

anti-IL6R LC
RLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPYTFGQGTKV

fused to SIRPa
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTA

TSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIG

NITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 317
DIQMTQSPSSLSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYTS

anti-IL6R LC
RLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPYTFGQGTKV

fused to TIM3
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNL

VPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTI

ENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFP

RMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRI

G

SEQ ID NO: 318
QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIGY

anti-IL6R HC
ISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLART

fused to PD1 ECD
TAMDYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD

ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLN

WYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARR

NDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQ

TLV

SEQ ID NO: 319
DIQMTQSPSSLSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYTS

anti-IL6R LC
RLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPYTFGQGTKV

fused to BTLA
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELEC

PVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPND

NGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 320
QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIGY

anti-IL6R HC
ISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLART

fused to
TAMDYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

SIGLEC10 ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD

ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYW

FKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQM

QDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVT

VICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDL

TCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYL

EAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVK

AGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLG

NGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRV

QVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSS

QASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGL

RLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 321
QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIGY

anti-IL6R HC
ISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLART

fused to SIRPa
TAMDYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD

ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGR

ELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGS

PDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 322
QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIGY

anti-IL6R HC
ISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLART

fused to TGFbR
TAMDYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD

ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKS

CMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAAS

PKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 323
QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIGY

anti-IL6R HC
ISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLART

fused to TIM3
TAMDYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD

ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGN

VVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPG

IMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGS

LPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 324
QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIGY

anti-IL6R HC
ISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLART

fused to VEGFR
TAMDYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD

ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDT

LIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTI

IDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVN

RDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVH

EK

SEQ ID NO: 325
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to BTLA
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLNGT

TCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTT

LYVTDVKSASERPSKDEMAS

SEQ ID NO: 326
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWFQQKPGQAPRPLIYDAS

anti-IL17R LC
TRATGVPARFSGSGSGTDFTLTISSLQSEDFAVYYCQQYDNWPLTFGGGTK

fused to PD1 ECD
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTE

GDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRV

TQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERR

AEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 327
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWFQQKPGQAPRPLIYDAS

anti-IL17R LC
TRATGVPARFSGSGSGTDFTLTISSLQSEDFAVYYCQQYDNWPLTFGGGTK

fused to
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

SIGLEC10 ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCS

FSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQL

TGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTAL

TQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTT

SHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISIS

RDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLS

SSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 328
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWFQQKPGQAPRPLIYDAS

anti-IL17R LC
TRATGVPARFSGSGSGTDFTLTISSLQSEDFAVYYCQQYDNWPLTFGGGTK

fused to SIRPa
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCT

ATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRI

GNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 329
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWFQQKPGQAPRPLIYDAS

anti-IL17R LC
TRATGVPARFSGSGSGTDFTLTISSLQSEDFAVYYCQQYDNWPLTFGGGTK

fused to TIM3
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGN

LVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSL

TIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAF

PRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRI

G

SEQ ID NO: 330
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to PD1 ECD
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNW

YRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRND

SGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTL

V

SEQ ID NO: 331
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWFQQKPGQAPRPLIYDAS

anti-IL17R LC
TRATGVPARFSGSGSGTDFTLTISSLQSEDFAVYYCQQYDNWPLTFGGGTK

fused to BTLA
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELE

CPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPN

DNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 332
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

SIGLEC10 ECD
EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFK

AVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQD

ESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVI

CVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTC

HVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEA

QKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAG

DSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGT

SLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVE

HEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASP

APSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRC

EAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 333
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to SIRPa
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGREL

IYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPD

DVEFKSGAGTELSVRAKPS

SEQ ID NO: 334
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to TGFbR
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCM

SNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPK

CIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 335
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to TIM3
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNV

VLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGI

MNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSL

PDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 336
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to VEGFR
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLI

PDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIID

VVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRD

LKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK

SEQ ID NO: 337
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDQTIHWMRQAPGQGLEWIG

anti-IL23 HC
YIYPRDDSPKYNENFKGKVTITADKSTSTAYMELSSLRSEDTAVYYCAIPDR

fused to BTLA
SGYAWFIYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLM

ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGG

GGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCK

LNGTTCVKLEDRQTSWKEEKNISFFILHEEPVLPNDNGSYRCSANFQSNLIE

SHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 338
DIQMTQSPSSLSASVGDRVTITCKASRDVAIAVAWYQQKPGKVPKLLIYWA

anti-IL23 LC
STRHTGVPSRFSGSGSRTDFTLTISSLQPEDVADYFCHQYSSYPFTFGSGTKL

fused to PD1 ECD
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEG

DNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVT

QLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRA

EVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 339
DIQMTQSPSSLSASVGDRVTITCKASRDVAIAVAWYQQKPGKVPKLLIYWA

anti-IL23 LC
STRHTGVPSRFSGSGSRTDFTLTISSLQPEDVADYFCHQYSSYPFTFGSGTKL

fused to
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

SIGLEC10 ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSF

SYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQL

TGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTAL

TQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTT

SHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISIS

RDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLS

SSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 340
DIQMTQSPSSLSASVGDRVTITCKASRDVAIAVAWYQQKPGKVPKLLIYWA

anti-IL23 LC
STRHTGVPSRFSGSGSRTDFTLTISSLQPEDVADYFCHQYSSYPFTFGSGTKL

fused to SIRPa
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTA

TSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIG

NITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 341
DIQMTQSPSSLSASVGDRVTITCKASRDVAIAVAWYQQKPGKVPKLLIYWA

anti-IL23 LC
STRHTGVPSRFSGSGSRTDFTLTISSLQPEDVADYFCHQYSSYPFTFGSGTKL

fused to TIM3
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNL

VPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTI

ENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFP

RMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRI

G

SEQ ID NO: 342
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDQTIHWMRQAPGQGLEWIG

anti-IL23 HC
YIYPRDDSPKYNENFKGKVTITADKSTSTAYMELSSLRSEDTAVYYCAIPDR

fused to PD1 ECD
SGYAWFIYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLM

ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGG

GGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFV

LNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRA

RRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQ

FQTLV

SEQ ID NO: 343
DIQMTQSPSSLSASVGDRVTITCKASRDVAIAVAWYQQKPGKVPKLLIYWA

anti-IL23 LC
STRHTGVPSRFSGSGSRTDFTLTISSLQPEDVADYFCHQYSSYPFTFGSGTKL

fused to BTLA
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELEC

PVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPND

NGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 344
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDQTIHWMRQAPGQGLEWIG

anti-IL23 HC
YIYPRDDSPKYNENFKGKVTITADKSTSTAYMELSSLRSEDTAVYYCAIPDR

fused to
SGYAWFIYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

SIGLEC10 ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLM

ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGG

GGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYG

YWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDA

QMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQ

PVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHN

TDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNV

PYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPG

VKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLEN

LGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELP

RVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSC

SSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSS

GLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 345
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDQTIHWMRQAPGQGLEWIG

anti-IL23 HC
YIYPRDDSPKYNENFKGKVTITADKSTSTAYMELSSLRSEDTAVYYCAIPDR

fused to SIRPa
SGYAWFIYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLM

ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGG

GGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGP

GRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFR

KGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 346
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDQTIHWMRQAPGQGLEWIG

anti-IL23 HC
YIYPRDDSPKYNENFKGKVTITADKSTSTAYMELSSLRSEDTAVYYCAIPDR

fused to TGFbR
SGYAWFIYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLM

ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGG

GGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQ

KSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDA

ASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 347
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDQTIHWMRQAPGQGLEWIG

anti-IL23 HC
YIYPRDDSPKYNENFKGKVTITADKSTSTAYMELSSLRSEDTAVYYCAIPDR

fused to TIM3
SGYAWFIYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLM

ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGG

GGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFEC

GNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQI

PGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTL

GSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 348
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDQTIHWMRQAPGQGLEWIG

anti-IL23 HC
YIYPRDDSPKYNENFKGKVTITADKSTSTAYMELSSLRSEDTAVYYCAIPDR

fused to VEGFR
SGYAWFIYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLM

ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGG

GGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFP

LDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQT

NTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKL

VNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVR

VHEK

SEQ ID NO: 349
QVQLVESGGGVVQPGRSLRLSCAASGFTFSVYGMNWVRQAPGKGLEWVA

anti-IL1b HC
IIWYDGDNQYYADSVKGRFTISRDNSKNTLYLQMNGLRAEDTAVYYCARD

fused to BTLA
LRTGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWC

KLNGTTCVKLEDRQTSWKEEKNISFFILHEEPVLPNDNGSYRCSANFQSNLI

ESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 350
EIVLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLIKYASQ

anti-IL1b LC
SFSGVPSRFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPFTFGPGTKVDI

fused to PD1 ECD
KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG

NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS

FNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDN

ATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQL

PNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEV

PTAHPSPSPRPAGQFQTLV

SEQ ID NO: 351
EIVLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLIKYASQ

anti-IL1b LC
SFSGVPSRFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPFTFGPGTKVDI

fused to
KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG

SIGLEC10 ECD
NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS

FNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSY

PRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTG

DPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQ

KPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSH

FSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRD

NTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSH

PWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRV

MVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVL

SPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGP

SCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPW

ANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 352
EIVLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLIKYASQ

anti-IL1b LC
SFSGVPSRFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPFTFGPGTKVDI

fused to SIRPa
KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG

ECD
NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS

FNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSL

IPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITP

ADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 353
EIVLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLIKYASQ

anti-IL1b LC
SFSGVPSRFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPFTFGPGTKVDI

fused to TIM3
KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG

ECD
NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS

FNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVP

VCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIEN

VTLADSGIYCCRIQIPGIVINDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRM

LTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 354
QVQLVESGGGVVQPGRSLRLSCAASGFTFSVYGMNWVRQAPGKGLEWVA

anti-IL1b HC
IIWYDGDNQYYADSVKGRFTISRDNSKNTLYLQMNGLRAEDTAVYYCARD

fused to PD1 ECD
LRTGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESF

VLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVR

ARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAG

QFQTLV

SEQ ID NO: 355
EIVLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPDQSPKLLIKYASQ

anti-IL1b LC
SFSGVPSRFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPFTFGPGTKVDI

fused to BTLA
KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG

ECD
NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS

FNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPV

KYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNG

SYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 356
QVQLVESGGGVVQPGRSLRLSCAASGFTFSVYGMNWVRQAPGKGLEWVA

anti-IL1b HC
IIWYDGDNQYYADSVKGRFTISRDNSKNTLYLQMNGLRAEDTAVYYCARD

fused to
LRTGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

SIGLEC10 ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAY

GYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRD

AQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPG

QPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDH

NTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGN

VPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELP

GVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLE

NLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLE

LPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHC

SCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLS

SGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 357
QVQLVESGGGVVQPGRSLRLSCAASGFTFSVYGMNWVRQAPGKGLEWVA

anti-IL1b HC
IIWYDGDNQYYADSVKGRFTISRDNSKNTLYLQMNGLRAEDTAVYYCARD

fused to SIRPa
LRTGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGA

GPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKF

RKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 358
QVQLVESGGGVVQPGRSLRLSCAASGFTFSVYGMNWVRQAPGKGLEWVA

anti-IL1b HC
IIWYDGDNQYYADSVKGRFTISRDNSKNTLYLQMNGLRAEDTAVYYCARD

fused to TGFbR
LRTGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDN

QKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILED

AASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 359
QVQLVESGGGVVQPGRSLRLSCAASGFTFSVYGMNWVRQAPGKGLEWVA

anti-IL1b HC
IIWYDGDNQYYADSVKGRFTISRDNSKNTLYLQMNGLRAEDTAVYYCARD

fused to TIM3
LRTGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVF

ECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCR

IQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLFERGHGPAETQ

TLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 360
QVQLVESGGGVVQPGRSLRLSCAASGFTFSVYGMNWVRQAPGKGLEWVA

anti-IL1b HC
IIWYDGDNQYYADSVKGRFTISRDNSKNTLYLQMNGLRAEDTAVYYCARD

fused to VEGFR
LRTGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKF

PLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQ

TNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKK

LVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFV

RVHEK

SEQ ID NO: 361
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anti-VEGF HC
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

fused to BTLA
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

ECD
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANR

PHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHEEPVLPNDNGSYRCSA

NFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 362
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTS

anti-VEGF LC
SLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKV

fused to PD1 ECD
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEG

DNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVT

QLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRA

EVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 363
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTS

anti-VEGF LC
SLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKV

fused to
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

SIGLEC10 ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSF

SYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQL

TGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTAL

TQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTT

SHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISIS

RDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLS

SSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 364
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTS

anti-VEGF LC
SLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKV

fused to SIRPa
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTA

TSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIG

NITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 365
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTS

anti- VEGF LC
SLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKV

fused to TIM3
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNL

VPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTI

ENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFP

RMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRI

G

SEQ ID NO: 366
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anti-VEGF HC
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

fused to PD1 ECD
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSF

SNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDF

HMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPS

PSPRPAGQFQTLV

SEQ ID NO: 367
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTS

anti-VEGF LC
SLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKV

fused to BTLA
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELEC

PVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPND

NGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 368
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anti-VEGF HC
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

fused to
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

SIGLEC10 ECD
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWT

GSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGN

CSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYI

PETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFT

PRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALE

PQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPR

PLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQA

NRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPS

DPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWE

AEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSL

SLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 369
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anti-VEGF HC
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

fused to SIRPa
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

ECD
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQ

WFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGT

YYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 370
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anti-VEGF HC
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

fused to TGFbR
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

ECD
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVR

FSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPY

HDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 371
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anti-VEGF HC
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

fused to TIM3
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

ECD
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGK

GACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADS

GIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGH

GPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 372
EVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSS

anti-VEGFR HC
ISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARVTD

fused to BTLA
AFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

ECD
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLN

GTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHS

TTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 373
DIQMTQSPSSVSASIGDRVTITCRASQGIDNWLGWYQQKPGKAPKLLIYDA

anti-VEGFR LC
SNLDTGVPSRFSGSGSGTYFTLTISSLQAEDFAVYFCQQAKAFPPTFGGGTK

fused to PD1 ECD
VDIKGTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTE

GDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRV

TQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERR

AEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 374
DIQMTQSPSSVSASIGDRVTITCRASQGIDNWLGWYQQKPGKAPKLLIYDA

anti-VEGFR LC
SNLDTGVPSRFSGSGSGTYFTLTISSLQAEDFAVYFCQQAKAFPPTFGGGTK

fused to
VDIKGTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

SIGLEC10 ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCS

FSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQL

TGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTAL

TQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTT

SHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISIS

RDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLS

SSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 375
DIQMTQSPSSVSASIGDRVTITCRASQGIDNWLGWYQQKPGKAPKLLIYDA

anti-VEGFR LC
SNLDTGVPSRFSGSGSGTYFTLTISSLQAEDFAVYFCQQAKAFPPTFGGGTK

fused to SIRPa
VDIKGTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCT

ATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRI

GNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 376
DIQMTQSPSSVSASIGDRVTITCRASQGIDNWLGWYQQKPGKAPKLLIYDA

anti-VEGFR LC
SNLDTGVPSRFSGSGSGTYFTLTISSLQAEDFAVYFCQQAKAFPPTFGGGTK

fused to TIM3
VDIKGTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGN

LVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSL

TIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAF

PRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRI

G

SEQ ID NO: 377
EVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSS

anti-VEGFR HC
ISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARVTD

fused to PD1 ECD
AFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLN

WYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARR

NDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQ

TLV

SEQ ID NO: 378
DIQMTQSPSSVSASIGDRVTITCRASQGIDNWLGWYQQKPGKAPKLLIYDA

anti-VEGFR LC
SNLDTGVPSRFSGSGSGTYFTLTISSLQAEDFAVYFCQQAKAFPPTFGGGTK

fused to BTLA
VDIKGTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELE

CPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPN

DNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 379
EVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSS

anti-VEGFR HC
ISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARVTD

fused to
AFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

SIGLEC10 ECD
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYW

FKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQM

QDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVT

VICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDL

TCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYL

EAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVK

AGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLG

NGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRV

QVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSS

QASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGL

RLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 380
EVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSS

anti-VEGFR HC
ISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARVTD

fused to SIRPa
AFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

ECD
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGR

ELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGS

PDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 381
EVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSS

anti-VEGFR HC
ISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARVTD

fused to TGFbR
AFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

ECD
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKS

CMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAAS

PKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 382
EVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSS

anti-VEGFR HC
ISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARVTD

fused to TIM3
AFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

ECD
VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGN

VVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPG

IMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGS

LPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 383
QVQLQQPGAELVKPGASVMMSCKASGYTFTNYNMHWVKQTPGQGLEWI

anti-CD47 HC
GTIYPGNDDTSYNQKFKDKATLTADKSSSAAYMQLSSLTSEDSAVYYCAR

fused to BTLA
GGYRAMDYWGQTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWC

KLNGTTCVKLEDRQTSWKEEKNISFFILHEEPVLPNDNGSYRCSANFQSNLI

ESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 384
DVLMTQTPLSLPVSLGDQASISCRSSQSIVYSNGNTYLGWYLQKPGQSPKL

anti-CD47 LC
LIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYHCFQGSHVPYTF

fused to PD1 ECD
GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK

VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ

GLSSPVTKSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPAL

LVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQD

CRFRVTQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELR

VTERRAEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 385
DVLMTQTPLSLPVSLGDQASISCRSSQSIVYSNGNTYLGWYLQKPGQSPKL

anti-CD47 LC
LIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYHCFQGSHVPYTF

fused to
GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK

SIGLEC10 ECD
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ

GLSSPVTKSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLC

ISVPCSFSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMST

RGRFQLTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFF

LKVTALTQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQ

GTKPTTSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPR

DLVISISRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVL

QNRVLSSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSV

QYPPENLRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLS

WTQRGQVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSV

HYSPKLLGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFE

VTPSSAGPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLI

ST

SEQ ID NO: 386
DVLMTQTPLSLPVSLGDQASISCRSSQSIVYSNGNTYLGWYLQKPGQSPKL

anti-CD47 LC
LIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYHCFQGSHVPYTF

fused to TIM3
GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK

ECD
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ

GLSSPVTKSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYT

PAAPGNLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFR

KGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQR

DFTAAFPRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRD

SGATIRIG

SEQ ID NO: 387
QVQLQQPGAELVKPGASVMNISCKASGYTFTNYNMHWVKQTPGQGLEWI

anti-CD47 HC
GTIYPGNDDTSYNQKFKDKATLTADKSSSAAYMQLSSLTSEDSAVYYCAR

fused to PD1 ECD
GGYRAMDYWGQTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESF

VLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVR

ARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAG

QFQTLV

SEQ ID NO: 388
DVLMTQTPLSLPVSLGDQASISCRSSQSIVYSNGNTYLGWYLQKPGQSPKL

anti-CD47 LC
LIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYHCFQGSHVPYTF

fused to BTLA
GGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK

ECD
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQ

GLSSPVTKSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAG

DPFELECPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHF

EPVLPNDNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 389
QVQLQQPGAELVKPGASVMMSCKASGYTFTNYNMHWVKQTPGQGLEWI

anti-CD47 HC
GTIYPGNDDTSYNQKFKDKATLTADKSSSAAYMQLSSLTSEDSAVYYCAR

fused to
GGYRAMDYWGQTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

SIGLEC10 ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAY

GYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRD

AQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPG

QPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDH

NTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGN

VPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELP

GVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLE

NLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLE

LPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHC

SCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLS

SGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 390
QVQLQQPGAELVKPGASVMMSCKASGYTFTNYNMHWVKQTPGQGLEWI

anti-CD47 HC
GTIYPGNDDTSYNQKFKDKATLTADKSSSAAYMQLSSLTSEDSAVYYCAR

fused to TGFbR
GGYRAMDYWGQTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDN

QKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILED

AASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 391
QVQLQQPGAELVKPGASVMNISCKASGYTFTNYNMHWVKQTPGQGLEWI

anti-CD47 HC
GTIYPGNDDTSYNQKFKDKATLTADKSSSAAYMQLSSLTSEDSAVYYCAR

fused to TIM3
GGYRAMDYWGQTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVF

ECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCR

IQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLFERGHGPAETQ

TLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 392
QVQLQQPGAELVKPGASVMMSCKASGYTFTNYNMHWVKQTPGQGLEWI

anti-CD47 HC
GTIYPGNDDTSYNQKFKDKATLTADKSSSAAYMQLSSLTSEDSAVYYCAR

fused to VEGFR
GGYRAMDYWGQTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

ECD
FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN

VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKF

PLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQ

TNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKK

LVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFV

RVHEK

SEQ ID NO: 393
QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSNVISWVRQAPGQGLEWMG

anti-TGFb HC
GVIPIVDIANYAQRFKGRVTITADESTSTTYMELSSLRSEDTAVYYCASTLG

fused to BTLA
LVLDAMDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTC

NVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGG

GSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKL

NGTTCVKLEDRQTSWKEEKNISFFILHEEPVLPNDNGSYRCSANFQSNLIES

HSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 394
ETVLTQSPGTLSLSPGERATLSCRASQSLGSSYLAWYQQKPGQAPRLLIYGA

anti-TGFb LC
SSRAPGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYADSPITFGQGTRL

fused to PD1 ECD
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEG

DNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVT

QLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRA

EVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 395
ETVLTQSPGTLSLSPGERATLSCRASQSLGSSYLAWYQQKPGQAPRLLIYGA

anti-TGFb LC
SSRAPGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYADSPITFGQGTRL

fused to
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

SIGLEC10 ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSF

SYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQL

TGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTAL

TQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTT

SHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISIS

RDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLS

SSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 396
ETVLTQSPGTLSLSPGERATLSCRASQSLGSSYLAWYQQKPGQAPRLLIYGA

anti-TGFb LC
SSRAPGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYADSPITFGQGTRL

fused to SIRPa
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTA

TSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIG

NITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 397
ETVLTQSPGTLSLSPGERATLSCRASQSLGSSYLAWYQQKPGQAPRLLIYGA

anti-TGFb LC
SSRAPGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYADSPITFGQGTRL

fused to TIM3
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNL

VPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTI

ENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFP

RMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRI

G

SEQ ID NO: 398
QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSNVISWVRQAPGQGLEWMG

anti-TGFb HC
GVIPIVDIANYAQRFKGRVTITADESTSTTYMELSSLRSEDTAVYYCASTLG

fused to PD1 ECD
LVLDAMDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD

YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTC

NVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGG

GSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVL

NWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRAR

RNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQF

QTLV

SEQ ID NO: 399
ETVLTQSPGTLSLSPGERATLSCRASQSLGSSYLAWYQQKPGQAPRLLIYGA

anti-TGFb LC
SSRAPGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYADSPITFGQGTRL

fused to BTLA
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELEC

PVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPND

NGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 400
QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSNVISWVRQAPGQGLEWMG

anti-TGFb HC
GVIPIVDIANYAQRFKGRVTITADESTSTTYMELSSLRSEDTAVYYCASTLG

fused to
LVLDAMDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD

SIGLEC10 ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTC

NVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGG

GSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGY

WFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQ

MQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQP

VTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNT

DLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVP

YLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGV

KAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENL

GNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPR

VQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCS

SQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSG

LRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 401
QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSNVISWVRQAPGQGLEWMG

anti-TGFb HC
GVIPIVDIANYAQRFKGRVTITADESTSTTYMELSSLRSEDTAVYYCASTLG

fused to SIRPa
LVLDAMDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTC

NVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGG

GSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPG

RELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRK

GSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 402
QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSNVISWVRQAPGQGLEWMG

anti-TGFb HC
GVIPIVDIANYAQRFKGRVTITADESTSTTYMELSSLRSEDTAVYYCASTLG

fused to TIM3
LVLDAMDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTC

NVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGG

GSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECG

NVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIP

GIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLG

SLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 403
QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSNVISWVRQAPGQGLEWMG

anti-TGFb HC
GVIPIVDIANYAQRFKGRVTITADESTSTTYMELSSLRSEDTAVYYCASTLG

fused to VEGFR
LVLDAMDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTC

NVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGG

GSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPL

DTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQT

NTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKL

VNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVR

VHEK

SEQ ID NO: 404
DVQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMG

anti-LAP HC
YISYDGTNNYNPSLKNRISITRDTSKHQFFLKLNSVTTEDTATYYCARSFYN

fused to BTLA
NYFDFWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLN

GTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHS

TTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 405
DVQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMG

anti-LAP HC
YISYDGTNNYNPSLKNRISITRDTSKHQFFLKLNSVTTEDTATYYCARSFYN

fused to PD1 ECD
NYFDFWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLN

WYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARR

NDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQ

TLV

SEQ ID NO: 406
DVQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMG

anti-LAP HC
YISYDGTNNYNPSLKNRISITRDTSKHQFFLKLNSVTTEDTATYYCARSFYN

fused to
NYFDFWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

SIGLEC10 ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYW

FKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQM

QDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVT

VICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDL

TCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYL

EAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVK

AGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLG

NGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRV

QVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSS

QASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGL

RLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 407
DVQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMG

anti-LAP HC
YISYDGTNNYNPSLKNRISITRDTSKHQFFLKLNSVTTEDTATYYCARSFYN

fused to SIRPa
NYFDFWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGR

ELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGS

PDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 408
DVQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMG

anti-LAP HC
YISYDGTNNYNPSLKNRISITRDTSKHQFFLKLNSVTTEDTATYYCARSFYN

fused to TIM3
NYFDFWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGN

VVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPG

IMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGS

LPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 409
DVQLQESGPGLVKPSQSLSLTCSVTGYSITSGYYWNWIRQFPGNKLEWMG

anti-LAP HC
YISYDGTNNYNPSLKNRISITRDTSKHQFFLKLNSVTTEDTATYYCARSFYN

fused to VEGFR
NYFDFWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

ECD
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDT

LIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTI

IDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVN

RDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVH

EK

SEQ ID NO: 410
QVQLVQPGAEVRKPGASVKVSCKASGYRFTSYYIDWVRQAPGQGLEWMG

anti-GARP HC
RIDPEDAGTKYAQKFQGRVTMTADTSTSTVYVELSSLRSEDTAVYYCARY

fused to BTLA
EWETVVVGDLMYEYEYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTA

ECD
ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPK

PKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQ

VYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGGG

GGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPH

VTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANF

QSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 411
QVQLVQPGAEVRKPGASVKVSCKASGYRFTSYYIDWVRQAPGQGLEWMG

anti-GARP HC
RIDPEDAGTKYAQKFQGRVTMTADTSTSTVYVELSSLRSEDTAVYYCARY

fused to PD1 ECD
EWETVVVGDLMYEYEYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTA

ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPK

PKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQ

VYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGGG

GGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSN

TSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHM

SVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSP

RPAGQFQTLV

SEQ ID NO: 412
QVQLVQPGAEVRKPGASVKVSCKASGYRFTSYYIDWVRQAPGQGLEWMG

anti-GARP HC
RIDPEDAGTKYAQKFQGRVTMTADTSTSTVYVELSSLRSEDTAVYYCARY

fused to
EWETVVVGDLMYEYEYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTA

SIGLEC10 ECD
ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPK

PKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQ

VYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGGG

GGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGS

TPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSL

VIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPET

LEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRP

QDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQP

QGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLG

LELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRT

VLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPG

VLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEG

LHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLH

GGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 413
QVQLVQPGAEVRKPGASVKVSCKASGYRFTSYYIDWVRQAPGQGLEWMG

anti-GARP HC
RIDPEDAGTKYAQKFQGRVTMTADTSTSTVYVELSSLRSEDTAVYYCARY

fused to SIRPa
EWETVVVGDLMYEYEYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTA

ECD
ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPK

PKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQ

VYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGGG

GGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQW

FRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYY

CVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 414
QVQLVQPGAEVRKPGASVKVSCKASGYRFTSYYIDWVRQAPGQGLEWMG

anti-GARP HC
RIDPEDAGTKYAQKFQGRVTMTADTSTSTVYVELSSLRSEDTAVYYCARY

fused to TIM3
EWETVVVGDLMYEYEYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTA

ECD
ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPK

PKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQ

VYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGGG

GGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGA

CPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGI

YCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGP

AETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 415
QVQLVQPGAEVRKPGASVKVSCKASGYRFTSYYIDWVRQAPGQGLEWMG

anti-GARP HC
RIDPEDAGTKYAQKFQGRVTMTADTSTSTVYVELSSLRSEDTAVYYCARY

fused to VEGFR
EWETVVVGDLMYEYEYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTA

ECD
ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPK

PKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQ

VYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGGG

GGSGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVT

LKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYL

THRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKH

QHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKK

NSTFVRVHEK

SEQ ID NO: 416
EVQLVQSGAEVKKPGESLKISCKASGYAFSSSWINWVRQMPGKGLEWMG

anti-CD73 HC
RIYPRAGDTNYAGKFKDQVTISADKSISTAYLQWSSLKASDTAMYYCASLL

fused to BTLA
DYSMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

ECD
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCK

LNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIE

SHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 417
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTS

anti-CD73 LC
RLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPLTFGQGTKVE

fused to PD1 ECD
IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS

GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK

SFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGD

NATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQ

LPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAE

VPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 418
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTS

anti-CD73 LC
RLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPLTFGQGTKVE

fused to
IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS

SIGLEC10 ECD
GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK

SFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFS

YPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLT

GDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALT

QKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTS

HFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISR

DNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSS

HPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLR

VMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQV

LSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLG

PSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGP

WANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 419
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTS

anti-CD73 LC
RLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPLTFGQGTKVE

fused to SIRPa
IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS

ECD
GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK

SFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATS

LIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNIT

PADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 420
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTS

anti-CD73 LC
RLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPLTFGQGTKVE

fused to TIM3
IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS

ECD
GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK

SFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLV

PVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIE

NVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPR

MLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 421
EVQLVQSGAEVKKPGESLKISCKASGYAFSSSWINWVRQMPGKGLEWMG

anti-CD73 HC
RIYPRAGDTNYAGKFKDQVTISADKSISTAYLQWSSLKASDTAMYYCASLL

fused to PD1 ECD
DYSMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFV

LNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRA

RRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQ

FQTLV

SEQ ID NO: 422
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYYTS

anti-CD73 LC
RLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPLTFGQGTKVE

fused to BTLA
IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS

ECD
GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK

SFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECP

VKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDN

GSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 423
EVQLVQSGAEVKKPGESLKISCKASGYAFSSSWINWVRQMPGKGLEWMG

anti-CD73 HC
RIYPRAGDTNYAGKFKDQVTISADKSISTAYLQWSSLKASDTAMYYCASLL

fused to
DYSMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

SIGLEC10 ECD
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYG

YWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDA

QMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQ

PVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHN

TDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNV

PYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPG

VKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLEN

LGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELP

RVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSC

SSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSS

GLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 424
EVQLVQSGAEVKKPGESLKISCKASGYAFSSSWINWVRQMPGKGLEWMG

anti-CD73 HC
RIYPRAGDTNYAGKFKDQVTISADKSISTAYLQWSSLKASDTAMYYCASLL

fused to SIRPa
DYSMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

ECD
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGP

GRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFR

KGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 425
EVQLVQSGAEVKKPGESLKISCKASGYAFSSSWINWVRQMPGKGLEWMG

anti-CD73 HC
RIYPRAGDTNYAGKFKDQVTISADKSISTAYLQWSSLKASDTAMYYCASLL

fused to TGFbR
DYSMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

ECD
PEPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQ

KSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDA

ASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 426
EVQLVQSGAEVKKPGESLKISCKASGYAFSSSWINWVRQMPGKGLEWMG

anti-CD73 HC
RIYPRAGDTNYAGKFKDQVTISADKSISTAYLQWSSLKASDTAMYYCASLL

fused to TIM3
DYSMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

ECD
PEPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFEC

GNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQI

PGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTL

GSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 427
EVQLVQSGAEVKKPGESLKISCKASGYAFSSSWINWVRQMPGKGLEWMG

anti-CD73 HC
RIYPRAGDTNYAGKFKDQVTISADKSISTAYLQWSSLKASDTAMYYCASLL

fused to VEGFR
DYSMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

ECD
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFP

LDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQT

NTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKL

VNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVR

VHEK

SEQ ID NO: 428
QVOLVOSGSELKKPGASVKVSCKASGYTFTHYGMNWVRQAPGQGLKWM

anti-CD39 HC
GWINTYTGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCARR

fused to BTLA
RYEGNYVFYYFDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGG

GGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPH

VTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANF

QSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 429
QVOLVOSGSELKKPGASVKVSCKASGYTFTHYGMNWVRQAPGQGLKWM

anti-CD39 HC
GWINTYTGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCARR

fused to PD1 ECD
RYEGNYVFYYFDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGG

GGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSN

TSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHM

SVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSP

RPAGQFQTLV

SEQ ID NO: 430
QVOLVOSGSELKKPGASVKVSCKASGYTFTHYGMNWVRQAPGQGLKWM

anti-CD39 HC
GWINTYTGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCARR

fused to
RYEGNYVFYYFDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

SIGLEC10 ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGG

GGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGS

TPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSL

VIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPET

LEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRP

QDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQP

QGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLG

LELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRT

VLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPG

VLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEG

LHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLH

GGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 431
QVOLVOSGSELKKPGASVKVSCKASGYTFTHYGMNWVRQAPGQGLKWM

anti-CD39 HC
GWINTYTGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCARR

fused to SIRPa
RYEGNYVFYYFDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGG

GGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQW

FRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYY

CVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 432
QVOLVOSGSELKKPGASVKVSCKASGYTFTHYGMNWVRQAPGQGLKWM

anti-CD39 HC
GWINTYTGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCARR

fused to TGFbR
RYEGNYVFYYFDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGG

GGSGGGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFS

TCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHD

FILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 433
QVOLVOSGSELKKPGASVKVSCKASGYTFTHYGMNWVRQAPGQGLKWM

anti-CD39 HC
GWINTYTGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCARR

fused to TIM3
RYEGNYVFYYFDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGG

GGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGA

CPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGI

YCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGP

AETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 434
QVOLVOSGSELKKPGASVKVSCKASGYTFTHYGMNWVRQAPGQGLKWM

anti-CD39 HC
GWINTYTGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCARR

fused to VEGFR
RYEGNYVFYYFDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGG

GGSGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVT

LKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYL

THRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKH

QHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKK

NSTFVRVHEK

SEQ ID NO: 435
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVT

anti-CTLA4 HC
FISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTG

fused to BTLA
WLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

ECD
PEPVTVSWNSGALTSGVHTFYAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAG

DPFELECPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHF

EPVLPNDNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 436
EIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQKPGQAPRLLIYGA

anti-CTLA4 LC
FSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTK

fused to PD1 ECD
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTE

GDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRV

TQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERR

AEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 437
EIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQKPGQAPRLLIYGA

anti-CTLA4 LC
FSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTK

fused to
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

SIGLEC10 ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCS

FSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQL

TGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTAL

TQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTT

SHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISIS

RDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLS

SSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 438
EIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQKPGQAPRLLIYGA

anti-CTLA4 LC
FSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTK

fused to SIRPa
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCT

ATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRI

GNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 439
EIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQKPGQAPRLLIYGA

anti-CTLA4 LC
FSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTK

fused to TIM3
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGN

LVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSL

TIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAF

PRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRI

G

SEQ ID NO: 440
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVT

anti-CTLA4 HC
FISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTG

fused to PD1 ECD
WLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPAL

LVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQD

CRFRVTQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELR

VTERRAEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 441
EIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQKPGQAPRLLIYGA

anti-CTLA4 LC
FSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTK

fused to BTLA
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELE

CPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPN

DNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 442
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVT

anti-CTLA4 HC
FISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTG

fused to
WLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

SIGLEC10 ECD
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLC

ISVPCSFSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMST

RGRFQLTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFF

LKVTALTQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQ

GTKPTTSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPR

DLVISISRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVL

QNRVLSSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSV

QYPPENLRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLS

WTQRGQVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSV

HYSPKLLGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFE

VTPSSAGPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLI

ST

SEQ ID NO: 443
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVT

anti-CTLA4 HC
FISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTG

fused to SIRPa
WLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

ECD
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETA

TLRCTATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNM

DFSIRIGNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 444
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVT

anti-CTLA4 HC
FISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTG

fused to TGFbR
WLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

ECD
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGGGGSGGGGSGGGGSTIPPHVQKSVNNDMIVTDNN

GAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDE

NITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECND

NIIFSEEYNTSNPD

SEQ ID NO: 445
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVT

anti-CTLA4 HC
FISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTG

fused to TIM3
WLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

ECD
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYT

PAAPGNLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFR

KGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQR

DFTAAFPRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRD

SGATIRIG

SEQ ID NO: 446
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVT

anti-CTLA4 HC
FISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTG

fused to VEGFR
WLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF

ECD
PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV

NHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGGGGSGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTE

GRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLL

TCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTE

LNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQ

GLYTCAASSGLMTKKNSTFVRVHEK

SEQ ID NO: 447
QVQLVQSGVEVKKPGASVKVSCKASGYTFTNYYMYWVRQAPGQGLEWM

anti-PD1 HC
GGINPSNGGTNFNEKFKNRVTLTTDSSTTTAYMELKSLQFDDTAVYYCARR

fused to BTLA
DYRFDMGFDYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVK

ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCK

LNGTTCVKLEDRQTSWKEEKNISFFILHEEPVLPNDNGSYRCSANFQSNLIE

SHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 448
EIVLTQSPATLSLSPGERATLSCRASKGVSTSGYSYLHWYQQKPGQAPRLLI

anti-PD1 LC
YLASYLESGVPARFSGSGSGTDFTLTISSLEPEDFAVYYCQHSRDLPLTFGG

fused to PD1 ECD
GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD

NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS

SPVTKSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVV

TEGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRF

RVTQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTE

RRAEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 449
EIVLTQSPATLSLSPGERATLSCRASKGVSTSGYSYLHWYQQKPGQAPRLLI

anti-PD1 LC
YLASYLESGVPARFSGSGSGTDFTLTISSLEPEDFAVYYCQHSRDLPLTFGG

fused to
GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD

SIGLEC10 ECD
NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS

SPVTKSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISV

PCSFSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGR

FQLTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKV

TALTQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTK

PTTSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLV

ISISRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNR

VLSSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPP

ENLRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQ

RGQVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSP

KLLGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSS

AGPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 450
EIVLTQSPATLSLSPGERATLSCRASKGVSTSGYSYLHWYQQKPGQAPRLLI

anti-PD1 LC
YLASYLESGVPARFSGSGSGTDFTLTISSLEPEDFAVYYCQHSRDLPLTFGG

fused to SIRPa
GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD

ECD
NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS

SPVTKSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLR

CTATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSI

RIGNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 451
EIVLTQSPATLSLSPGERATLSCRASKGVSTSGYSYLHWYQQKPGQAPRLLI

anti-PD1 LC
YLASYLESGVPARFSGSGSGTDFTLTISSLEPEDFAVYYCQHSRDLPLTFGG

fused to TIM3
GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD

ECD
NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS

SPVTKSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAA

PGNLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGD

VSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFT

AAFPRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGA

TIRIG

SEQ ID NO: 452
QVQLVQSGVEVKKPGASVKVSCKASGYTFTNYYMYWVRQAPGQGLEWM

anti-PD1 HC
GGINPSNGGTNFNEKFKNRVTLTTDSSTTTAYMELKSLQFDDTAVYYCARR

fused to PD1 ECD
DYRFDMGFDYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFV

LNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRA

RRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQ

FQTLV

SEQ ID NO: 453
EIVLTQSPATLSLSPGERATLSCRASKGVSTSGYSYLHWYQQKPGQAPRLLI

anti-PD1 LC
YLASYLESGVPARFSGSGSGTDFTLTISSLEPEDFAVYYCQHSRDLPLTFGG

fused to BTLA
GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD

ECD
NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLS

SPVTKSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPF

ELECPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHEEPV

LPNDNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 454
QVQLVQSGVEVKKPGASVKVSCKASGYTFTNYYMYWVRQAPGQGLEWM

anti-PD1 HC
GGINPSNGGTNFNEKFKNRVTLTTDSSTTTAYMELKSLQFDDTAVYYCARR

fused to
DYRFDMGFDYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVK

SIGLEC10 ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYG

YWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDA

QMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQ

PVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHN

TDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNV

PYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPG

VKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLEN

LGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELP

RVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSC

SSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSS

GLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 455
QVQLVQSGVEVKKPGASVKVSCKASGYTFTNYYMYWVRQAPGQGLEWM

anti-PD1 HC
GGINPSNGGTNFNEKFKNRVTLTTDSSTTTAYMELKSLQFDDTAVYYCARR

fused to SIRPa
DYRFDMGFDYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVK

ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGP

GRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFR

KGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 456
QVQLVQSGVEVKKPGASVKVSCKASGYTFTNYYMYWVRQAPGQGLEWM

anti-PD1 HC
GGINPSNGGTNFNEKFKNRVTLTTDSSTTTAYMELKSLQFDDTAVYYCARR

fused to TGFbR
DYRFDMGFDYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVK

ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQ

KSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDA

ASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 457
QVQLVQSGVEVKKPGASVKVSCKASGYTFTNYYMYWVRQAPGQGLEWM

anti-PD1 HC
GGINPSNGGTNFNEKFKNRVTLTTDSSTTTAYMELKSLQFDDTAVYYCARR

fused to TIM3
DYRFDMGFDYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVK

ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFEC

GNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQI

PGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTL

GSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 458
QVQLVQSGVEVKKPGASVKVSCKASGYTFTNYYMYWVRQAPGQGLEWM

anti-PD1 HC
GGINPSNGGTNFNEKFKNRVTLTTDSSTTTAYMELKSLQFDDTAVYYCARR

fused to VEGFR
DYRFDMGFDYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVK

ECD
DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFP

LDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQT

NTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKL

VNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVR

VHEK

SEQ ID NO: 459
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1 HC
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

fused to BTLA
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWC

KLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLI

ESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 460
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-PDL1 LC
SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTK

fused to
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

SIGLEC10 ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCS

FSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQL

TGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTAL

TQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTT

SHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISIS

RDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLS

SSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 461
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-PDL1 LC
SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTK

fused to SIRPa
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCT

ATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRI

GNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 462
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-PDL1 LC
SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTK

fused to TIM3
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGN

LVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSL

TIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAF

PRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRI

G

SEQ ID NO: 463
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1 HC
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

fused to
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

SIGLEC10 ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAY

GYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRD

AQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPG

QPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDH

NTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGN

VPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELP

GVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLE

NLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLE

LPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHC

SCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLS

SGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 464
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-PDL1 LC
SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTK

fused to BTLA
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELE

CPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPN

DNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 465
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1 HC
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

fused to SIRPa
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGA

GPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKF

RKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 466
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1 HC
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

fused to TGFbR
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDN

QKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILED

AASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 467
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1 HC
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

fused to TIM3
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVF

ECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCR

IQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLIIRGHGPAETQ

TLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 468
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1 HC
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

fused to VEGFR
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKF

PLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQ

TNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKK

LVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFV

RVHEK

SEQ ID NO: 469
EVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLG

anti-TIGIT HC
KTYYRFKWYSDYAVSVKGRITINPDTSKNQFSLQLNSVTPEDTAVFYCTRE

fused to BTLA
STTYDLLAGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGG

GGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPH

VTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANF

QSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 470
DIVMTQSPDSLAVSLGERATINCKSSQTVLYSSNNKKYLAWYQQKPGQPPN

anti-TIGIT LC
LLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPFT

fused to PD1 ECD
FGPGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQW

KVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH

QGLSSPVTKSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPA

LLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQ

DCRFRVTQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAEL

RVTERRAEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 471
DIVMTQSPDSLAVSLGERATINCKSSQTVLYSSNNKKYLAWYQQKPGQPPN

anti-TIGIT LC
LLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPFT

fused to
FGPGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQW

SIGLEC10 ECD
KVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH

QGLSSPVTKSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGL

CISVPCSFSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMS

TRGRFQLTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGF

FLKVTALTQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSS

QGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAP

RDLVISISRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVL

QNRVLSSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSV

QYPPENLRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLS

WTQRGQVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSV

HYSPKLLGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSEE

VTPSSAGPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLI

ST

SEQ ID NO: 472
DIVMTQSPDSLAVSLGERATINCKSSQTVLYSSNNKKYLAWYQQKPGQPPN

anti-TIGIT LC
LLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPFT

fused to SIRPa
FGPGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQW

ECD
KVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH

QGLSSPVTKSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGET

ATLRCTATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNN

MDFSIRIGNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 473
DIVMTQSPDSLAVSLGERATINCKSSQTVLYSSNNKKYLAWYQQKPGQPPN

anti-TIGIT LC
LLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPFT

fused to TIM3
FGPGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQW

ECD
KVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH

QGLSSPVTKSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFY

TPAAPGNLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFR

KGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQR

DFTAAFPRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRD

SGATIRIG

SEQ ID NO: 474
EVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLG

anti-TIGIT HC
KTYYRFKWYSDYAVSVKGRITINPDTSKNQFSLQLNSVTPEDTAVFYCTRE

fused to PD1 ECD
STTYDLLAGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGG

GGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSN

TSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHM

SVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSP

RPAGQFQTLV

SEQ ID NO: 475
DIVMTQSPDSLAVSLGERATINCKSSQTVLYSSNNKKYLAWYQQKPGQPPN

anti-TIGIT LC
LLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPFT

fused to BTLA
FGPGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQW

ECD
KVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH

QGLSSPVTKSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILA

GDPFELECPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILH

FEPVLPNDNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 476
EVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLG

anti-TIGIT HC
KTYYRFKWYSDYAVSVKGRITINPDTSKNQFSLQLNSVTPEDTAVFYCTRE

fused to
STTYDLLAGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

SIGLEC10 ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGG

GGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGS

TPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSL

VIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPET

LEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRP

QDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQP

QGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLG

LELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRT

VLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPG

VLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEG

LHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLH

GGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 477
EVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLG

anti-TIGIT HC
KTYYRFKWYSDYAVSVKGRITINPDTSKNQFSLQLNSVTPEDTAVFYCTRE

fused to SIRPa
STTYDLLAGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGG

GGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQW

FRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYY

CVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 478
EVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLG

anti-TIGIT HC
KTYYRFKWYSDYAVSVKGRITINPDTSKNQFSLQLNSVTPEDTAVFYCTRE

fused to TGFbR
STTYDLLAGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGG

GGSGGGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFS

TCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHD

FILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 479
EVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLG

anti-TIGIT HC
KTYYRFKWYSDYAVSVKGRITINPDTSKNQFSLQLNSVTPEDTAVFYCTRE

fused to TIM3
STTYDLLAGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGG

GGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGA

CPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGI

YCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGP

AETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 480
EVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLG

anti-TIGIT HC
KTYYRFKWYSDYAVSVKGRITINPDTSKNQFSLQLNSVTPEDTAVFYCTRE

fused to VEGFR
STTYDLLAGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGG

GGSGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVT

LKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYL

THRQTNTI1DVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKH

QHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKK

NSTFVRVHEK

SEQ ID NO: 481
QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIY

anti-TIM3 HC
DVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCSSYADSVVFGGG

fused to BTLA
TKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKAD

ECD
SSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTV

EKTVAPTECSGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFEL

ECPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLP

NDNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 482
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA

anti-TIM3 LC
ISVSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKAN

fused to PD1 ECD
WGFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVL

NWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRAR

RNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQF

QTLV

SEQ ID NO: 483
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA

anti-TIM3 LC
ISVSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKAN

fused to
WGFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

SIGLEC10 ECD
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGY

WFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQ

MQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQP

VTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNT

DLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVP

YLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGV

KAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENL

GNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPR

VQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCS

SQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSG

LRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 484
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA

anti-TIM3 LC
ISVSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKAN

fused to SIRPa
WGFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPG

RELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRK

GSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 485
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA

anti-TIM3 LC
ISVSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKAN

fused to TIM3
WGFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECG

NVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIP

GIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLG

SLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 486
QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIY

anti-TIM3 HC
DVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCSSYADSVVFGGG

fused to PD1 ECD
TKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKAD

SSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTV

EKTVAPTECSGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTE

GDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRV

TQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERR

AEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 487
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA

anti-TIM3 LC
ISVSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKAN

fused to BTLA
WGFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKL

NGTTCVKLEDRQTSWKEEKNISFFILHEEPVLPNDNGSYRCSANFQSNLIES

HSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 488
QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIY

anti-TIM3 HC
DVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCSSYADSVVFGGG

fused to
TKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKAD

SIGLEC10 ECD
SSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTV

EKTVAPTECSGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPC

SFSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQ

LTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTA

LTQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPT

TSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISI

SRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVL

SSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 489
QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIY

anti-TIM3 HC
DVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCSSYADSVVFGGG

fused to SIRPa
TKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKAD

ECD
SSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTV

EKTVAPTECSGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCT

ATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRI

GNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 490
QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIY

anti-TIM3 HC
DVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCSSYADSVVFGGG

fused to TGFbR
TKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKAD

ECD
SSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTV

EKTVAPTECSGGGGSGGGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKF

PQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLE

TVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSE

EYNTSNPD

SEQ ID NO: 491
QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIY

anti-TIM3 HC
DVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCSSYADSVVFGGG

fused to TIM3
TKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKAD

ECD
SSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTV

EKTVAPTECSGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPG

NLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVS

LTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAA

FPRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATI

RIG

SEQ ID NO: 492
QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIY

anti-TIM3 HC
DVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCSSYADSVVFGGG

fused to VEGFR
TKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKAD

ECD
SSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTV

EKTVAPTECSGGGGSGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELV

IPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEAT

VNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGI

DFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYT

CAASSGLMTKKNSTFVRVHEK

SEQ ID NO: 493
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQSPEKGLEWIGEI

anti-41BB HC
NHGGYVTYNPSLESRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDYGPG

fused to BTLA
NYDWYFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTC

NVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGG

GSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKL

NGTTCVKLEDRQTSWKEEKNISFFILHEEPVLPNDNGSYRCSANFQSNLIES

HSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 494
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDAS

anti-41BB LC
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPALTFCGGT

fused to PD1 ECD
KVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA

LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP

VTKSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVT

EGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFR

VTQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTER

RAEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 495
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDAS

anti-41BB LC
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPALTFCGGT

fused to
KVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA

SIGLEC10 ECD
LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP

VTKSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPC

SFSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQ

LTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTA

LTQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPT

TSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISI

SRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVL

SSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 496
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDAS

anti-41BB LC
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPALTFCGGT

fused to SIRPa
KVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA

ECD
LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP

VTKSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRC

TATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIR

IGNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 497
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDAS

anti-41BB LC
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPALTFCGGT

fused to TIM3
KVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA

ECD
LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP

VTKSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPG

NLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVS

LTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAA

FPRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATT

RIG

SEQ ID NO: 498
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQSPEKGLEWIGEI

anti-41BB HC
NHGGYVTYNPSLESRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDYGPG

fused to PD1 ECD
NYDWYFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD

YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTC

NVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGG

GSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVL

NWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRAR

RNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQF

QTLV

SEQ ID NO: 499
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDAS

anti-41BB LC
NRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPALTFCGGT

fused to BTLA
KVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA

ECD
LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP

VTKSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFEL

ECPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLP

NDNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 500
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQSPEKGLEWIGEI

anti-41BB HC
NHGGYVTYNPSLESRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDYGPG

fused to
NYDWYFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD

SIGLEC10 ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTC

NVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGG

GSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGY

WFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQ

MQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQP

VTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNT

DLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVP

YLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGV

KAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENL

GNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPR

VQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCS

SQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSG

LRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 501
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQSPEKGLEWIGEI

anti-41BB HC
NHGGYVTYNPSLESRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDYGPG

fused to SIRPa
NYDWYFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD

EC
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTC

NVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGG

GSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPG

RELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRK

GSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 502
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQSPEKGLEWIGEI

anti-41BB HC
NHGGYVTYNPSLESRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDYGPG

fused to TGFbR
NYDWYFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTC

NVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGG

GSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQK

SCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAA

SPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 503
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQSPEKGLEWIGEI

anti-41BB HC
NHGGYVTYNPSLESRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDYGPG

fused to TIM3
NYDWYFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTC

NVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGG

GSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECG

NVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIP

GIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLG

SLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 504
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQSPEKGLEWIGEI

anti-41BB HC
NHGGYVTYNPSLESRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDYGPG

fused to VEGFR
NYDWYFDLWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTC

NVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGG

GSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPL

DTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQT

NTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKL

VNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVR

VHEK

SEQ ID NO: 505
QVQLVQSGSELKKPGASVKVSCKASGYTFTDYSMHWVRQAPGQGLKWM

anti-OX40 HC
GWINTETGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCANP

fused to BTLA
YYDYVSYYAMDYWGOGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKFIPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANR

PHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHEEPVLPNDNGSYRCSA

NFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 506
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-OX40 LC
SYLYTGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCOQHYSTPRTFGQGTKL

fused to PD1 ECD
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEG

DNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVT

QLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRA

EVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 507
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-OX40 LC
SYLYTGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCOQHYSTPRTFGQGTKL

fused to
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

SIGLEC10 ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSF

SYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQL

TGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTAL

TQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTT

SHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISIS

RDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLS

SSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 508
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-OX40 LC
SYLYTGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCOQHYSTPRTFGQGTKL

fused to SIRPa
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTA

TSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIG

NITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 509
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-OX40 LC
SYLYTGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCOQHYSTPRTFGQGTKL

fused to TIM3
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNL

VPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTI

ENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFP

RMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRI

G

SEQ ID NO: 510
QVQLVQSGSELKKPGASVKVSCKASGYTFTDYSMHWVRQAPGQGLKWM

anti-OX40 HC
GWINTETGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCANP

fused to PD1 ECD
YYDYVSYYAMDYWGOGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSF

SNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDF

HMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPS

PSPRPAGQFQTLV

SEQ ID NO: 511
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-OX40 LC
SYLYTGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCOQHYSTPRTFGQGTKL

fused to BTLA
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELEC

PVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPND

NGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 512
QVQLVQSGSELKKPGASVKVSCKASGYTFTDYSMHWVRQAPGQGLKWM

anti-OX40 HC
GWINTETGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCANP

fused to
YYDYVSYYAMDYWGOGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

SIGLEC10 ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWT

GSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGN

CSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYI

PETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFT

PRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALE

PQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPR

PLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQA

NRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPS

DPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWE

AEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSL

SLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 513
QVQLVQSGSELKKPGASVKVSCKASGYTFTDYSMHWVRQAPGQGLKWM

anti-OX40 HC
GWINTETGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCANP

fused to SIRPa
YYDYVSYYAMDYWGOGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQ

WFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGT

YYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 514
QVQLVQSGSELKKPGASVKVSCKASGYTFTDYSMHWVRQAPGQGLKWM

anti-OX40 HC
GWINTETGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCANP

fused to TGFbR
YYDYVSYYAMDYWGOGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVR

FSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPY

HDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 515
QVQLVQSGSELKKPGASVKVSCKASGYTFTDYSMHWVRQAPGQGLKWM

anti-OX40 HC
GWINTETGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCANP

fused to TIM3
YYDYVSYYAMDYWGOGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGK

GACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADS

GIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGH

GPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 516
QVQLVQSGSELKKPGASVKVSCKASGYTFTDYSMHWVRQAPGQGLKWM

anti-OX40 HC
GWINTETGEPTYADDFKGRFVFSLDTSVSTAYLQISSLKAEDTAVYYCANP

fused to VEGFR
YYDYVSYYAMDYWGOGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

ECD
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNIT

VTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTN

YLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSS

KHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMT

KKNSTFVRVHEK

SEQ ID NO: 517
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDYAMHWVRQAPGQGLEWM

anti-ICOS HC
GLISIYSDHTNYNQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCGRN

fused to BTLA
NYGNYGWYFDVWGQGTTVTVSSGGGGSGGGGSGGGGSKESCDVQLYIKR

ECD
QSEHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEE

KNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSK

DEMAS

SEQ ID NO: 518
EIVLTQSPATLSLSPGERATLSCSASSSVSYMHWYQQKPGQAPRLLIYDTSK

anti-ICOS LC
LASGIPARFSGSGSGTDYTLTISSLEPEDFAVYYCFQGSGYPYTFGOGTKLEI

fused to PD1 ECD
KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG

NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS

FNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDN

ATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQL

PNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEV

PTAHPSPSPRPAGQFQTLV

SEQ ID NO: 519
EIVLTQSPATLSLSPGERATLSCSASSSVSYMHWYQQKPGQAPRLLIYDTSK

anti-ICOS LC
LASGIPARFSGSGSGTDYTLTISSLEPEDFAVYYCFQGSGYPYTFGOGTKLEI

fused to
KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG

SIGLEC10 ECD
NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS

FNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSY

PRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTG

DPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQ

KPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSH

FSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRD

NTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSH

PWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRV

MVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVL

SPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGP

SCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPW

ANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 520
EIVLTQSPATLSLSPGERATLSCSASSSVSYMHWYQQKPGQAPRLLIYDTSK

anti-ICOS LC
LASGIPARFSGSGSGTDYTLTISSLEPEDFAVYYCFQGSGYPYTFGOGTKLEI

fused to SIRPa
KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG

EC
NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS

FNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSL

IPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITP

ADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 521
EIVLTQSPATLSLSPGERATLSCSASSSVSYMHWYQQKPGQAPRLLIYDTSK

anti-ICOS LC
LASGIPARFSGSGSGTDYTLTISSLEPEDFAVYYCFQGSGYPYTFGOGTKLEI

fused to TIM3
KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG

ECD
NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS

FNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVP

VCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIEN

VTLADSGIYCCRIQIPG1MNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRM

LTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 522
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDYAMHWVRQAPGQGLEWM

anti-ICOS HC
GLISIYSDHTNYNQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCGRN

fused to PD1 ECD
NYGNYGWYFDVWGQGTTVTVSSGGGGSGGGGSGGGGSPGWFLDSPDRP

WNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAF

PEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKA

QIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 523
EIVLTQSPATLSLSPGERATLSCSASSSVSYMHWYQQKPGQAPRLLIYDTSK

anti-ICOS LC
LASGIPARFSGSGSGTDYTLTISSLEPEDFAVYYCFQGSGYPYTFGOGTKLEI

fused to BTLA
KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG

ECD
NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS

FNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPV

KYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNG

SYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 524
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDYAMHWVRQAPGQGLEWM

anti-ICOS HC
GLISIYSDHTNYNQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCGRN

fused to
NYGNYGWYFDVWGQGTTVTVSSGGGGSGGGGSGGGGSMDGRFWIRVQE

SIGLEC10 ECD
SVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNH

QSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVR

YNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFS

WTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTV

RLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQ

PPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGS

QQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCV

THSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLG

SQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELL

EGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSI

LQLPDKKGLIST

SEQ ID NO: 525
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDYAMHWVRQAPGQGLEWM

anti-ICOS HC
GUSTYSDHTNYNQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCGRN

fused to SIRPa
NYGNYGWYFDVWGQGTTVTVSSGGGGSGGGGSGGGGSEEELQVIQPDKS

ECD
VLVAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVS

DLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVR

AKPS

SEQ ID NO: 526
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDYAMHWVRQAPGQGLEWM

anti-ICOS HC
GLISIYSDHTNYNQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCGRN

fused to TGFbR
NYGNYGWYFDVWGQGTTVTVSSGGGGSGGGGSGGGGSTIPPHVQKSVNN

ECD
DMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVCV

AVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMC

SCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 527
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDYAMHWVRQAPGQGLEWM

anti-ICOS HC
GLISIYSDHTNYNQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCGRN

fused to TIM3
NYGNYGWYFDVWGQGTTVTVSSGGGGSGGGGSGGGGSSEVEYRAEVGQ

ECD
NAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSR

YWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAK

VTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRD

SRLANDLRDSGATIRIG

SEQ ID NO: 528
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDYAMHWVRQAPGQGLEWM

anti-ICOS HC
GLISIYSDHTNYNQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCGRN

fused to VEGFR
NYGNYGWYFDVWGQGTTVTVSSGGGGSGGGGSGGGGSSDTGRPFVEMY

ECD
SEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIIS

NATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEK

LVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLST

LTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK

SEQ ID NO: 529
KESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVK

BTLAecd-Fc-
LEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTTLYVT

PD1ecd
DVKSASERPSKDEMASASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLN

WYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARR

NDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQ

TLV

SEQ ID NO: 530
KESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVK

BTLAecd-Fc-
LEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTTLYVT

SIGLEC10ecd
DVKSASERPSKDEMASASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYW

FKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQM

QDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVT

VICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDL

TCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYL

EAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVK

AGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLG

NGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRV

QVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSS

QASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGL

RLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 531
KESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVK

BTLAecd-Fc-
LEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTTLYVT

SIRPaecd
DVKSASERPSKDEMASASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGR

ELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGS

PDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 532
KESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVK

BTLAecd-Fc-
LEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTTLYVT

TGFbRecd
DVKSASERPSKDEMASASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKS

CMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAAS

PKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 533
KESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVK

BTLAecd-Fc-
LEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTTLYVT

TIM3ecd
DVKSASERPSKDEMASASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGN

VVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPG

IMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGS

LPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 534
KESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVK

BTLAecd-Fc-
LEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTTLYVT

VEGFRecd
DVKSASERPSKDEMASASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDT

LIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTI

IDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVN

RDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVH

EK

SEQ ID NO: 535
PGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMS

PD1ecd-Fc-
PSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTY

BTLAecd
LCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLVAST

KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP

AVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDK

THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK

FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYP

SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC

SVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSKESCDVQLYIKRQ

SEHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEK

NISFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKD

EMAS

SEQ ID NO: 536
PGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMS

PD1ecd-Fc-
PSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTY

SIGLEC10ecd
LCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLVAST

KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP

AVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDK

THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK

FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYP

SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC

SVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSMDGRFWIRVQES

VMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQ

SREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRY

NFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSW

TGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVR

LRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPP

ATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQ

RALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTH

SSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQ

HVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEG

NSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQ

LPDKKGLIST

SEQ ID NO: 537
PGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMS

PD1ecd-Fc-
PSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTY

SIRPaecd
LCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLVAST

KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP

AVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDK

THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK

FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYP

SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC

SVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSEEELQVIQPDKSV

LVAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSD

LTKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRA

KPS

SEQ ID NO: 538
PGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMS

PD1ecd-Fc-
PSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTY

TGFbRecd
LCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLVAST

KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP

AVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDK

THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK

FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYP

SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC

SVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSTIPPHVQKSVNND

MIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVCVA

VWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCS

CSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 539
PGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMS

PD1ecd-Fc-
PSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTY

TIM3ecd
LCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLVAST

KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP

AVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDK

THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK

FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYP

SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC

SVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSSEVEYRAEVGQN

AYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRY

WLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKV

TPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDS

RLANDLRDSGATIRIG

SEQ ID NO: 540
PGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMS

PD1ecd-Fc-
PSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTY

VEGFRecd
LCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLVAST

KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFP

AVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDK

THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK

FNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYP

SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC

SVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSSDTGRPFVEMYSE

IPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISN

ATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKL

VLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTL

TIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK

SEQ ID NO: 541
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10ecd-
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

Fc-BTLAecd
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLISTASTKGPSVFPLAPSSKSTSGGTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVT

WCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQS

NLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 542
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10ecd-
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

Fc-PD1ecd
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLISTASTKGPSVFPLAPSSKSTSGGTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTS

ESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSV

VRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRP

AGQFQTLV

SEQ ID NO: 543
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10ecd-
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

Fc-SIRPaecd
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLISTASTKGPSVFPLAPSSKSTSGGTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRG

AGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCV

KFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 544
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10ecd-
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

Fc-TGFbRecd
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLISTASTKGPSVFPLAPSSKSTSGGTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTC

DNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFIL

EDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 545
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10ecd-
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

Fc-TIM3ecd
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLISTASTKGPSVFPLAPSSKSTSGGTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACP

VFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYC

CRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAE

TQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 546
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10ecd-
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

Fc-VEGFRecd
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLISTASTKGPSVFPLAPSSKSTSGGTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI

CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGG

SGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLK

KFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTH

RQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQH

KKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNS

TFVRVHEK

SEQ ID NO: 547
EEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQ

SIRPaecd-Fc-
KEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVE

BTLAecd
FKSGAGTELSVRAKPSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLN

GTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHS

TTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 548
EEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQ

SIRPaecd-Fc-
KEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVE

PD1ecd
FKSGAGTELSVRAKPSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLN

WYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARR

NDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQ

TLV

SEQ ID NO: 549
EEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQ

SIRPaecd-Fc-
KEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVE

SIGLEC10ecd
FKSGAGTELSVRAKPSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYW

FKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQM

QDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVT

VICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDL

TCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYL

EAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVK

AGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLG

NGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRV

QVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSS

QASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGL

RLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 550
EEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQ

SIRPaecd-Fc-
KEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVE

TGFbRecd
FKSGAGTELSVRAKPSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKS

CMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAAS

PKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 551
EEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQ

SIRPaecd-Fc-
KEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVE

TIM3ecd
FKSGAGTELSVRAKPSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGN

VVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPG

IMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGS

LPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 552
EEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQ

SIRPaecd-Fc-
KEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVE

VEGFRec
FKSGAGTELSVRAKPSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH

KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV

LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDT

LIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTI

IDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVN

RDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVH

EK

SEQ ID NO: 553
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbRecd-Fc-
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

BTLAecd
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDASTKGPSVFPLAPSSKSTS

GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT

KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN

YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS

LSLSPGKGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPV

KYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNG

SYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 554
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbRecd-Fc-
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

PD1ecd
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDASTKGPSVFPLAPSSKSTS

GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT

KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN

YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS

LSLSPGKGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGD

NATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQ

LPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAE

VPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 555
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbRecd-Fc-
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

SIGLEC10ecd
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDASTKGPSVFPLAPSSKSTS

GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT

KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN

YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS

LSLSPGKGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSY

PRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTG

DPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQ

KPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSH

FSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRD

NTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSH

PWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRV

MVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVL

SPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGP

SCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPW

ANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 556
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbRecd-Fc-
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

SIRPaecd
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDASTKGPSVFPLAPSSKSTS

GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT

KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN

YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS

LSLSPGKGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATS

LIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNIT

PADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 557
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbRecd-Fc-
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

TIM3ecd
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDASTKGPSVFPLAPSSKSTS

GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT

KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN

YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS

LSLSPGKGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLV

PVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIE

NVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPR

MLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 558
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbRecd-Fc-
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

VEGFRecd
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDASTKGPSVFPLAPSSKSTS

GGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT

KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN

YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS

LSLSPGKGGGGSGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPC

RVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVN

GHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDF

NWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCA

ASSGLMTKKNSTFVRVHEK

SEQ ID NO: 559
SEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRT

TIM3ecd-Fc-
DERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDE

BTLAecd
KFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINL

TQISTLANELRDSRLANDLRDSGATIRIGASTKGPSVFPLAPSSKSTSGGTAA

LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

KGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCAN

RPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCS

ANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 560
SEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRT

TIM3ecd-Fc-
DERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDE

PD1ecd
KFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINL

TQISTLANELRDSRLANDLRDSGATIRIGASTKGPSVFPLAPSSKSTSGGTAA

LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

KGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTC

SFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRD

FHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHP

SPSPRPAGQFQTLV

SEQ ID NO: 561
SEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRT

TIM3ecd-Fc-
DERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDE

SIGLEC10ecd
KFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINL

TQISTLANELRDSRLANDLRDSGATIRIGASTKGPSVFPLAPSSKSTSGGTAA

LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

KGGGGSGGGGSGGGGSMDGRFW1RVQESVMVPEGLCISVPCSFSYPRQDW

TGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKG

NCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVY

IPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSF

TPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPAL

EPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGP

RPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQ

ANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQP

SDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSW

EAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSS

LSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 562
SEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRT

TIM3ecd-Fc-
DERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDE

SIRPaecd
KFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINL

TQISTLANELRDSRLANDLRDSGATIRIGASTKGPSVFPLAPSSKSTSGGTAA

LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

KGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPI

QWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAG

TYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 563
SEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRT

TIM3ecd-Fc-
DERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDE

TGFbRecd
KFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINL

TQISTLANELRDSRLANDLRDSGATIRIGASTKGPSVFPLAPSSKSTSGGTAA

LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

KGGGGSGGGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDV

RFSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLP

YHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 564
SEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRT

TIM3ecd-Fc-
DERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDE

VEGFRecd
KFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINL

TQISTLANELRDSRLANDLRDSGATIRIGASTKGPSVFPLAPSSKSTSGGTAA

LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

KGGGGSGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNI

TVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKT

NYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPS

SKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLM

TKKNSTFVRVHEK

SEQ ID NO: 565
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFRecd-Fc -
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

BTLAecd
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKASTK

GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSKESCDVQLYIKRQS

EHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNI

SFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEM

AS

SEQ ID NO: 566
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFRecd-Fc -
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

PD1ecd
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKASTK

GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSPGWFLDSPDRPWN

PPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPED

RSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKE

SLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 567
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFRecd-Fc-
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

SIGLEC10ecd
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKASTK

GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSMDGRFWIRVQESV

MVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQS

REVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYN

FMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWT

GAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRL

RVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPP

ATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQ

RALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTH

SSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQ

HVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEG

NSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQ

LPDKKGLIST

SEQ ID NO: 568
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFRecd-Fc-
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

SIRPaecd
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKASTK

GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSEEELQVIQPDKSVL

VAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDL

TKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAK

PS

SEQ ID NO: 569
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFRecd-Fc-
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

TGFbRecd
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKASTK

GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSTIPPHVQKSVNND

MIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVCVA

VWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCS

CSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 570
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFRecd-Fc -
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

TIM3ecd
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKASTK

GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSSEVEYRAEVGQNA

YLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYW

LNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTP

APTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRL

ANDLRDSGATIRIG

SEQ ID NO: 571
KESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVK

BTLAecd-Fc-
LEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTTLYVT

IL12ecd
DVKSASERPSKDEMASASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDH

KPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVL

HQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLT

VDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGG

GSIWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLG

SGKTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQK

EPKNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQGVTCGA

ATLSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHKLKYEN

YTSSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCV

QVQGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEWASV

PCSGGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQNLLRAVSNMLQK

ARQTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITN

GSCLASRKTSFMNIALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQ

NMLAVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAVTID

RVMSYLNAS

SEQ ID NO: 572
IWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSG

IL12ecd-Fc-
KTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEP

BTLAecd
KNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQGVTCGAAT

LSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHKLKYENYT

SSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQV

QGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEWASVPCS

GGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKAR

QTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITNGSC

LASRKTSFMNIALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNML

AVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAVTIDRV

MSYLNASASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSG

ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVD

KRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

QEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNG

KEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL

VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE

GNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSKESCDV

QLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVKLEDRQT

SWKEEKNISFFILHEEPVLPNDNGSYRCSANFQSNLIESHSTTLYVTDVKSAS

ERPSKDEMAS

SEQ ID NO: 573
KESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVK

BTLAecd-Fc-
LEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTTLYVT

IL15ecd
DVKSASERPSKDEMASASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDH

KPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVL

HQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLT

VDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGG

GSNWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVI

SLESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSF

VHIVQMFINTS

SEQ ID NO: 574
NWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVISL

IL15ecd-Fc-
ESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVH

BTLAecd
IVQMFINTSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS

GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKV

DKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV

SQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN

GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC

LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ

EGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSKESCDV

QLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVKLEDRQT

SWKEEKNISFFILHEEPVLPNDNGSYRCSANFQSNLIESHSTTLYVTDVKSAS

ERPSKDEMAS

SEQ ID NO: 575
PGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMS

PD1ecd-Fc-
PSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTY

IL12ecd
LCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLVAST

KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPC

PSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWY

VDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKG

LPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE

ALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSIWELKKDVYVVELDWYP

DAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSGKTLTIQVKEFGDAGQYTC

HKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEPKNKTFLRCEAKNYSGRFT

CWWLTTISTDLTFSVKSSRGSSDPQGVTCGAATLSAERVRGDNKEYEYSVE

CQEDSACPAAEESLPIEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKNLQLKP

LKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQVQGKSKREKKDRVFTDKTS

ATVICRKNASISVRAQDRYYSSSWSEWASVPCSGGGGSGGGGSGGGGSRN

LPVATPDPGMFPCLHHSQNLLRAVSNMLQKARQTLEFYPCTSEEIDHEDIT

KDKTSTVEACLPLELTKNESCLNSRETSFITNGSCLASRKTSFMMALCLSSIY

EDLKMYQVEFKTMNAKLLMDPKRQIFLDQNMLAVIDELMQALNFNSETV

PQKSSLEEPDFYKTKIKLCILLHAFRIRAVTIDRVMSYLNAS

SEQ ID NO: 576
IWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSG

IL12ecd-Fc-
KTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEP

PD1ecd
KNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQGVTCGAAT

LSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHKLKYENYT

SSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQV

QGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEWASVPCS

GGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKAR

QTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITNGSC

LASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNML

AVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAVTIDRV

MSYLNASASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSG

ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVD

KRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

QEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNG

KEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL

VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE

GNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSPGWFLD

SPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQTD

KLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTYLCGAIS

LAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 577
PGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMS

PD1ecd-Fc-
PSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTY

IL15ecd
LCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLVAST

KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPC

PSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWY

VDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKG

LPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE

ALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSNWVNVISDLKKIEDLIQS

MHIDATLYTESDVHPSCKVTAMKCFLLELQVISLESGDASIHDTVENLIILA

NNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVHIVQMFINTS

SEQ ID NO: 578
NWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVISL

IL15ecd-Fc-
ESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVH

PD1ecd
IVQMFINTSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS

GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKV

DKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV

SQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN

GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC

LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ

EGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSPGWFL

DSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQT

DKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTYLCGAI

SLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 579
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10ecd-
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

Fc-IL12ecd
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLISTASTKGPSVFPLAPCSRSTSESTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSIWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLD

QSSEVLGSGKTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWST

DILKDQKEPKNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQ

GVTCGAATLSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVH

KLKYENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTWSTPHSY

FSLTFCVQVQGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSW

SEWASVPCSGGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQNLLRAV

SNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSR

ETSFITNGSCLASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAKLLMDPKR

QIFLDQNMLAVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRI

RAVTIDRVMSYLNAS

SEQ ID NO: 580
IWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSG

IL12ecd-Fc-
KTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEP

SIGLEC10ecd
KNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQGVTCGAAT

LSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHKLKYENYT

SSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQV

QGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEWASVPCS

GGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKAR

QTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITNGSC

LASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNML

AVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAVTIDRV

MSYLNASASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSG

ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVD

KRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

QEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNG

KEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL

VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE

GNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSMDGRFW

IRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTETTKGAPV

ATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQYFFRVERG

SYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFNWAFEECP

PPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSA

QRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQFLRLLCA

ADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRYTCRAEN

RLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVLEGQSLC

LVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGEFTCHAR

HPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSLRWWLG

EELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAWNVHGAQ

SGSILQLPDKKGLIST

SEQ ID NO: 581
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10ecd-
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

Fc-IL15ecd
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLISTASTKGPSVFPLAPCSRSTSESTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSNWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCF

LLELQVISLESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNI

KEFLQSFVHIVQMFINTS

SEQ ID NO: 582
NWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVISL

IL15ecd-Fc-
ESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVH

SIGLEC10ecd
IVQMFINTSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS

GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKV

DKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV

SQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN

GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC

LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ

EGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSMDGRF

WIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTETTKGA

PVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQYFFRVE

RGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFNWAFEE

CPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDFSRKGV

SAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQFLRLL

CAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRYTCRA

ENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVLEGQS

LCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGEFTCH

ARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSLRWW

LGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAWNVHG

AQSGSILQLPDKKGLIST

SEQ ID NO: 583
EEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQ

SIRPaecd-Fc-
KEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVE

IL12ecd
FKSGAGTELSVRAKPSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDH

KPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVL

HQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLT

VDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGG

GSIWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLG

SGKTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQK

EPKNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQGVTCGA

ATLSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHKLKYEN

YTSSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCV

QVQGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEWASV

PCSGGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQNLLRAVSNMLQK

ARQTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITN

GSCLASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQ

NMLAVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAVTID

RVMSYLNAS

SEQ ID NO: 584
IWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSG

IL12ecd-Fc-
KTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEP

SIRPaecd
KNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQGVTCGAAT

LSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHKLKYENYT

SSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQV

QGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEWASVPCS

GGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKAR

QTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITNGSC

LASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNML

AVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAVTIDRV

MSYLNASASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSG

ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVD

KRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

QEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNG

KEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL

VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE

GNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSEEELQVI

QPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPR

VTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVEFKSGAGT

ELSVRAKPS

SEQ ID NO: 585
EEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQ

SIRPaecd-Fc-
KEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVE

IL15ecd
FKSGAGTELSVRAKPSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDH

KPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVL

HQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLT

VDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGG

GSNWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVI

SLESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSF

VHIVQMFINTS

SEQ ID NO: 586
NWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVISL

IL15ecd-Fc-
ESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVH

SIRPaecd
IVQMFINTSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS

GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKV

DKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV

SQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN

GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC

LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ

EGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSEEELQV

IQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQKEGHFP

RVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVEFKSGAG

TELSVRAKPS

SEQ ID NO: 587
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbRecd-Fc-
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

IL12ecd
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDASTKGPSVFPLAPCSRSTS

ESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR

EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQP

REPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSL

GKGGGGSGGGGSGGGGSIWELKKDVYVVELDWYPDAPGEMVVLTCDTPE

EDGITWTLDQSSEVLGSGKTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLH

KKEDGIWSTDILKDQKEPKNKIFLRCEAKNYSGRFTCWWLTTISTDLTFSV

KSSRGSSDPQGVTCGAATLSAERVRGDNKEYEYSVECQEDSACPAAEESLP

IEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYP

DTWSTPHSYFSLTFCVQVQGKSKREKKDRVFTDKTSATVICRKNASISVRA

QDRYYSSSWSEWASVPCSGGGGSGGGGSGGGGSRNLPVATPDPGMFPCLH

HSQNLLRAVSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELT

KNESCLNSRETSFITNGSCLASRKTSFMMALCLSSIYEDLKMYQVEFKTMN

AKLLMDPKRQIFLDQNMLAVIDELMQALNFNSETVPQKSSLEEPDFYKTKI

KLCILLHAFRIRAVTIDRVMSYLNAS

SEQ ID NO: 588
IWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSG

IL12ecd-Fc-
KTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEP

TGFbRecd
KNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQGVTCGAAT

LSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHKLKYENYT

SSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQV

QGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEWASVPCS

GGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKAR

QTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITNGSC

LASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNML

AVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAVTIDRV

MSYLNASASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSG

ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVD

KRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

QEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNG

KEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL

VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE

GNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSTIPPHVQ

KSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKP

QEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGE

TFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 589
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbRecd-Fc-
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

IL15ecd
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDASTKGPSVFPLAPCSRSTS

ESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR

EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQP

REPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSL

GKGGGGSGGGGSGGGGSNWVNVISDLKKIEDLIQSMHIDATLYTESDVHPS

CKVTAMKCFLLELQVISLESGDASIHDTVENLIILANNSLSSNGNVTESGCK

ECEELEEKNIKEFLQSFVHIVQMFINTS

SEQ ID NO: 590
NWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVISL

IL15ecd-Fc-
ESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVH

TGFbRecd
IVQMFINTSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS

GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKV

DKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV

SQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN

GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC

LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ

EGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSTIPPHV

QKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEK

PQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPG

ETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 591
SEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRT

TIM3ecd-Fc-
DERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDE

IL12ecd
KFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINL

TQISTLANELRDSRLANDLRDSGATIRIGASTKGPSVFPLAPCSRSTSESTAA

LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQV

YTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGG

GGSGGGGSGGGGSIWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGI

TWTLDQSSEVLGSGKTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKE

DGIWSTDILKDQKEPKNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSS

RGSSDPQGVTCGAATLSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEV

MVDAVHKLKYENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDT

WSTPHSYFSLTFCVQVQGKSKREKKDRVFTDKTSATVICRKNASISVRAQD

RYYSSSWSEWASVPCSGGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHS

QNLLRAVSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKN

ESCLNSRETSFITNGSCLASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAK

LLMDPKRQIFLDQNMLAVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKL

CILLHAFRIRAVTIDRVMSYLNAS

SEQ ID NO: 592
IWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSG

IL12ecd-Fc-
KTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEP

TIM3ecd
KNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQGVTCGAAT

LSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHKLKYENYT

SSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQV

QGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEWASVPCS

GGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKAR

QTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITNGSC

LASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNML

AVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAVTIDRV

MSYLNASASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSG

ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVD

KRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

QEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNG

KEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL

VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE

GNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSSEVEYRA

EVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRTDERDVNY

WTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVI

KPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINLTQISTLAN

ELRDSRLANDLRDSGATIRIG

SEQ ID NO: 593
SEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRT

TIM3ecd-Fc-
DERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDE

IL15ecd
KFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINL

TQISTLANELRDSRLANDLRDSGATIRIGASTKGPSVFPLAPCSRSTSESTAA

LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQV

YTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGG

GGSGGGGSGGGGSNWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVT

AMKCFLLELQVISLESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEEL

EEKNIKEFLQSFVHIVQMFINTS

SEQ ID NO: 594
NWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVISL

IL15ecd-Fc-
ESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVH

TIM3ecd
IVQMFINTSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS

GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKV

DKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV

SQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN

GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC

LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ

EGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSSEVEYR

AEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRTDERDVN

YWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKL

VIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINLTQISTL

ANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 595
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFRecd-Fc-
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

IL12ecd
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKASTK

GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHIFPAV

LQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPS

CPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYV

DGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL

PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE

ALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSIWELKKDVYVVELDWYP

DAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSGKTLTIQVKEFGDAGQYTC

HKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEPKNKTFLRCEAKNYSGRFT

CWWLTTISTDLTFSVKSSRGSSDPQGVTCGAATLSAERVRGDNKEYEYSVE

CQEDSACPAAEESLPIEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKNLQLKP

LKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQVQGKSKREKKDRVFTDKTS

ATVICRKNASISVRAQDRYYSSSWSEWASVPCSGGGGSGGGGSGGGGSRN

LPVATPDPGMFPCLHHSQNLLRAVSNMLQKARQTLEFYPCTSEEIDHEDIT

KDKTSTVEACLPLELTKNESCLNSRETSFITNGSCLASRKTSFMMALCLSSIY

EDLKMYQVEFKTMNAKLLMDPKRQIFLDQNMLAVIDELMQALNFNSETV

PQKSSLEEPDFYKTKIKLCILLHAFRIRAVTIDRVMSYLNAS

SEQ ID NO: 596
IWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSG

IL12ecd-Fc-
KTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEP

VEGFRecd
KNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQGVTCGAAT

LSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHKLKYENYT

SSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQV

QGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEWASVPCS

GGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKAR

QTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITNGSC

LASRKTSFMNIALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNML

AVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAVTIDRV

MSYLNASASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSG

ALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVD

KRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

QEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNG

KEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL

VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE

GNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSSDTGRPF

VEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSR

KGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIEL

SVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMK

KFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK

SEQ ID NO: 597
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFRecd-Fc-
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

IL15ecd
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKASTK

GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV

LQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPS

CPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYV

DGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL

PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE

ALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSNWVNVISDLKKIEDLIQS

MHIDATLYTESDVHPSCKVTAMKCFLLELQVISLESGDASIHDTVENLIILA

NNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVHIVQMFINTS

SEQ ID NO: 598
NWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVISL

IL15ecd-Fc-
ESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVH

VEGFRecd
IVQMFINTSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS

GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKV

DKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV

SQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN

GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC

LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ

EGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSSDTGRP

FVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDS

RKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIE

LSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEM

KKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK

SEQ ID NO: 599
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10ecd-
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

Fc-41BBLecd
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLISTASTKGPSVFPLAPCSRSTSESTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSACPWAVSGARASPGSAASPRLREGPELSPDDPAGLLDLRQGM

FAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVY

YVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEA

RNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTP

EIPAGLPSPRSE

SEQ ID NO: 600
ACPWAVSGARASPGSAASPRLREGPELSPDDPAGLLDLRQGMFAQLVAQN

41BBLecd-Fc-
VLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLEL

SIGLEC10ecd
RRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQ

GRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLPSP

RSEASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG

VHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVES

KYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPE

VQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYK

CKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGF

YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVF

SCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSMDGRFWIRVQ

ESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATN

HQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYV

RYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSF

SWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRT

VRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADS

QPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLG

SQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVC

VTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPL

GSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEEL

LEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGS

ILQLPDKKGLIST

SEQ ID NO: 601
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10ecd-
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

Fc-CD30Lecd
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLISTASTKGPSVFPLAPCSRSTSESTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSQRTDSIPNSPDNVPLKGGNCSEDLLCILKRAPFKKSWAYLQVA

KHLNKTKLSWNKDGILHGVRYQDGNLVIQFPGLYFIICQLQFLVQCPNNSV

DLKLELLINKHIKKQALVTVCESGMQTKHVYQNLSQFLLDYLQVNTTISVN

VDTFQYIDTSTFPLENVLSIFLYSNSD

SEQ ID NO: 602
QRTDSIPNSPDNVPLKGGNCSEDLLCILKRAPFKKSWAYLQVAKHLNKTKL

CD30Lecd-Fc-
SWNKDGILHGVRYQDGNLVIQFPGLYFIICQLQFLVQCPNNSVDLKLELLIN

SIGLEC10ecd
KHIKKQALVTVCESGMQTKHVYQNLSQFLLDYLQVNTTISVNVDTFQYIDT

STFPLENVLSIFLYSNSDASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPE

PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVD

HKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLT

VLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSR

LTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSG

GGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFK

AVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQD

ESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVI

CVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTC

HVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEA

QKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAG

DSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGT

SLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVE

HEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASP

APSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRC

EAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 603
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10ecd-
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

Fc-CD40Lecd
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLISTASTKGPSVFPLAPCSRSTSESTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSGDQNPQIAAHVISEASSKTTSVLQWAEKGYYTMSNNLVTLEN

GKQLTVKRQGLYYIYAQVTFCSNREASSQAPFIASLCLKSPGRFERILLRAA

NTHSSAKPCGQQSIHLGGVFELQPGASVFVNVTDPSQVSHGTGFTSFGLLK

L

SEQ ID NO: 604
GDQNPQIAAHVISEASSKTTSVLQWAEKGYYTMSNNLVTLENGKQLTVKR

CD40Lecd-Fc-
QGLYYIYAQVTFCSNREASSQAPFIASLCLKSPGRFERILLRAANTHSSAKPC

SIGLEC10ecd
GQQSIHLGGVFELQPGASVFVNVTDPSQVSHGTGFTSFGLLKLASTKGPSVF

PLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG

LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPE

FLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEV

HNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEK

TISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNH

YTQKSLSLSLGKGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISV

PCSFSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGR

FQLTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKV

TALTQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTK

PTTSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLV

ISISRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNR

VLSSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPP

ENLRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQ

RGQVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSP

KLLGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSS

AGPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 605
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10ecd-
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

Fc-CD70ecd
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLISTASTKGPSVFPLAPCSRSTSESTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSQRFAQAQQQLPLESLGWDVAELQLNHTGPQQDPRLYWQGGP

ALGRSFLHGPELDKGQLRIHRDGIYMVHIQVTLAICSSTTASRHHPTTLAVG

ICSPASRSISLLRLSFHQGCTIASQRLTPLARGDTLCTNLTGTLLPSRNTDETF

FGVQWVRP

SEQ ID NO: 606
QRFAQAQQQLPLESLGWDVAELQLNHTGPQQDPRLYWQGGPALGRSFLH

CD70ecd-Fc-
GPELDKGQLRIHRDGIYMVHIQVTLAICSSTTASRHHPTTLAVGICSPASRSI

SIGLEC10ecd
SLLRLSFHQGCTIASQRLTPLARGDTLCTNLTGTLLPSRNTDETFFGVQWVR

PASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVH

TFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKY

GPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQF

NWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCS

VMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSMDGRFWIRVQESV

MVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQS

REVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYN

FMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWT

GAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRL

RVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPP

ATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQ

RALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTH

SSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQ

HVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEG

NSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQ

LPDKKGLIST

SEQ ID NO: 607
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10ecd-
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

Fc-GITRLecd
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLISTASTKGPSVFPLAPCSRSTSESTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSQLETAKEPCMAKFGPLPSKWQMASSEPPCVNKVSDWKLEILQ

NGLYLIYGQVAPNANYNDVAPFEVRLYKNKDMIQTLTNKSKIQNVGGTYE

LHVGDTIDLIFNSEHQVLKNNTYWGIILLANPQFIS

SEQ ID NO: 608
QLETAKEPCMAKFGPLPSKWQMASSEPPCVNKVSDWKLEILQNGLYLIYG

GITRLecd-Fc-
QVAPNANYNDVAPFEVRLYKNKDMIQTLTNKSKIQNVGGTYELHVGDTID

SIGLEC10ecd
LIFNSEHQVLKNNTYWGIILLANPQFISASTKGPSVFPLAPCSRSTSESTAAL

GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQV

YTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGG

GGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGS

TPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSL

VIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPET

LEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRP

QDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQP

QGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLG

LELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRT

VLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPG

VLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEG

LHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLH

GGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 609
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10ecd-
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

Fc-ICOSLecd
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLISTASTKGPSVFPLAPCSRSTSESTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSDTQEKEVRAMVGSDVELSCACPEGSRFDLNDVYVYWQTSES

KTVVTYHIPQNSSLENVDSRYRNRALMSPAGMLRGDFSLRLFNVTPQDEQ

KFHCLVLSQSLGFQEVLSVEVTLHVAANFSVPVVSAPHSPSQDELTFTCTSI

NGYPRPNVYWINKTDNSLLDQALQNDTVFLNMRGLYDVVSVLRIARTPSV

NIGCCIENVLLQQNLTVGSQTGNDIGERDKITENPVSTGEKNAATWS

SEQ ID NO: 610
DTQEKEVRAMVGSDVELSCACPEGSRFDLNDVYVYWQTSESKTVVTYHIP

ICOSLecd-Fc-
QNSSLENVDSRYRNRALMSPAGMLRGDFSLRLFNVTPQDEQKFHCLVLSQ

SIGLEC10ec
SLGFQEVLSVEVTLHVAANFSVPVVSAPHSPSQDELTFTCTSINGYPRPNVY

WINKTDNSLLDQALQNDTVFLNMRGLYDVVSVLRIARTPSVNIGCCIENVL

LQQNLTVGSQTGNDIGERDKITENPVSTGEKNAATWSASTKGPSVFPLAPC

SRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHITPAVLQSSGLYSLS

SVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNA

KTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISK

AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQK

SLSLSLGKGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFS

YPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLT

GDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALT

QKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTS

HFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISR

DNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSS

HPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLR

VMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQV

LSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLG

PSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGP

WANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 611
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10ecd-
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

Fc-LIGHTecd
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLISTASTKGPSVFPLAPCSRSTSESTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSDGPAGSWEQLIQERRSHEVNPAAHLTGANSSLTGSGGPLLWE

TQLGLAFLRGLSYHDGALVVTKAGYYYIYSKVQLGGVGCPLGLASTITHG

LYKRTPRYPEELELLVSQQSPCGRATSSSRVWWDSSFLGGVVHLEAGEKV

VVRVLDERLVRLRDGTRSYFGAFMV

SEQ ID NO: 612
DGPAGSWEQLIQERRSHEVNPAAHLTGANSSLTGSGGPLLWETQLGLAFLR

LIGHTecd-Fc-
GLSYHDGALVVTKAGYYYIYSKVQLGGVGCPLGLASTITHGLYKRTPRYP

SIGLEC10ecd
EELELLVSQQSPCGRATSSSRVWWDSSFLGGVVHLEAGEKVVVRVLDERL

VRLRDGTRSYFGAFMVASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDH

KPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVL

HQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLT

VDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGG

GSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAV

TETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDES

QYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICV

FNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHV

DFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQK

GQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDS

GRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSL

PVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEH

EGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPA

PSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCE

AWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 613
MDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTE

SIGLEC10ecd-
TTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQY

Fc-OX40Lecd
FFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFN

WAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDF

SRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQ

FLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRY

TCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVL

EGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGE

FTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSL

RWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAW

NVHGAQSGSILQLPDKKGLISTASTKGPSVFPLAPCSRSTSESTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYT

CNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV

SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPS

QEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGG

GGSGGGGSQVSHRYPRIQSIKVQFTEYKKEKGFILTSQKEDEIMKVQNNSVI

INCDGFYLISLKGYFSQEVNISLHYQKDEEPLFQLKKVRSVNSLMVASLTYK

DKVYLNVTTDNTSLDDFHVNGGELILIHQNPGEFCVL

SEQ ID NO: 614
QVSHRYPRIQSIKVQFTEYKKEKGFILTSQKEDEIMKVQNNSVIINCDGFYLI

OX40Lecd-Fc-
SLKGYFSQEVNISLHYQKDEEPLFQLKKVRSVNSLMVASLTYKDKVYLNV

SIGLEC10ecd
TTDNTSLDDFHVNGGELILIHQNPGEFCVLASTKGPSVFPLAPCSRSTSESTA

ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPK

PKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQ

VYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKG

GGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTG

STPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCS

LVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPE

TLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPR

PQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQ

PQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPL

GLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANR

TVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDP

GVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAE

GLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSL

HGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 615
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbRecd-Fc-
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

41BBLecd
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDASTKGPSVFPLAPCSRSTS

ESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR

EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQP

REPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSL

GKGGGGSGGGGSGGGGSACPWAVSGARASPGSAASPRLREGPELSPDDPA

GLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKE

LVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALT

VDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGA

TVLGLFRVTPEIPAGLPSPRSE

SEQ ID NO: 616
ACPWAVSGARASPGSAASPRLREGPELSPDDPAGLLDLRQGMFAQLVAQN

41BBLecd-Fc-
VLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLEL

TGFbRecd
RRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQ

GRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLPSP

RSEASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG

VHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVES

KYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPE

VQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYK

CKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGF

YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVF

SCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSTIPPHVQKSVN

NDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVC

VAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFM

CSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 617
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbRecd-Fc-
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

CD30Lecd
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDASTKGPSVFPLAPCSRSTS

ESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR

EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQP

REPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSL

GKGGGGSGGGGSGGGGSQRTDSIPNSPDNVPLKGGNCSEDLLCILKRAPFK

KSWAYLQVAKHLNKTKLSWNKDGILHGVRYQDGNLVIQFPGLYFIICQLQ

FLVQCPNNSVDLKLELLINKHIKKQALVTVCESGMQTKHVYQNLSQFLLD

YLQVNTTISVNVDTFQYIDTSTFPLENVLSIFLYSNSD

SEQ ID NO: 618
QRTDSIPNSPDNVPLKGGNCSEDLLCILKRAPFKKSWAYLQVAKHLNKTKL

CD30Lecd-Fc-
SWNKDGILHGVRYQDGNLVIQFPGLYFIICQLQFLVQCPNNSVDLKLELLIN

TGFbRecd
KHIKKQALVTVCESGMQTKHVYQNLSQFLLDYLQVNTTISVNVDTFQYIDT

STFPLENVLSIFLYSNSDASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPE

PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVD

HKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLT

VLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSR

LTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSG

GGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCM

SNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPK

CIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 619
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbRecd-Fc-
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

CD40Lecd
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDASTKGPSVFPLAPCSRSTS

ESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR

EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQP

REPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSL

GKGGGGSGGGGSGGGGSGDQNPQIAAHVISEASSKTTSVLQWAEKGYYT

MSNNLVTLENGKQLTVKRQGLYYIYAQVTFCSNREASSQAPFIASLCLKSP

GRFERILLRAANTHSSAKPCGQQSIHLGGVFELQPGASVFVNVTDPSQVSH

GTGFTSFGLLKL

SEQ ID NO: 620
GDQNPQIAAHVISEASSKTTSVLQWAEKGYYTMSNNLVTLENGKQLTVKR

CD40Lecd-Fc-
QGLYYIYAQVTFCSNREASSQAPFIASLCLKSPGRFERILLRAANTHSSAKPC

TGFbRecd
GQQSIHLGGVFELQPGASVFVNVTDPSQVSHGTGFTSFGLLKLASTKGPSVF

PLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG

LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPE

FLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEV

HNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEK

TISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNH

YTQKSLSLSLGKGGGGSGGGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAV

KFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDENIT

LETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNII

FSEEYNTSNPD

SEQ ID NO: 621
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbRecd-Fc-
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

CD70ecd
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDASTKGPSVFPLAPCSRSTS

ESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR

EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQP

REPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSL

GKGGGGSGGGGSGGGGSQRFAQAQQQLPLESLGWDVAELQLNHTGPQQD

PRLYWQGGPALGRSFLHGPELDKGQLRIHRDGIYMVHIQVTLAICSSTTASR

HHPFILAVGICSPASRSISLLRLSFHQGCTIASQRLTPLARGDTLCTNLTGTL

LPSRNTDETFFGVQWVRP

SEQ ID NO: 622
QRFAQAQQQLPLESLGWDVAELQLNHTGPQQDPRLYWQGGPALGRSFLH

CD70ecd-Fc-
GPELDKGQLRIHRDGIYMVHIQVTLAICSSTTASRHHPTTLAVGICSPASRSI

TGFbRecd
SLLRLSFHQGCTIASQRLTPLARGDTLCTNLTGTLLPSRNTDETFFGVQWVR

PASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVH

TFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKY

GPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQF

NWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCS

VMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSTIPPHVQKSVNND

MIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVCVA

VWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCS

CSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 623
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbRecd-Fc-
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

GITRLecd
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDASTKGPSVFPLAPCSRSTS

ESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR

EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQP

REPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSL

GKGGGGSGGGGSGGGGSQLETAKEPCMAKFGPLPSKWQMASSEPPCVNK

VSDWKLEILQNGLYLIYGQVAPNANYNDVAPFEVRLYKNKDMIQTLTNKS

KIQNVGGTYELHVGDTIDLIFNSEHQVLKNNTYWGIILLANPQFIS

SEQ ID NO: 624
QLETAKEPCMAKFGPLPSKWQMASSEPPCVNKVSDWKLEILQNGLYLIYG

GITRLecd-Fc-
QVAPNANYNDVAPFEVRLYKNKDMIQTLTNKSKIQNVGGTYELHVGDTID

TGFbRecd
LIFNSEHQVLKNNTYWGIILLANPQFISASTKGPSVFPLAPCSRSTSESTAAL

GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQV

YTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGG

GGSGGGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFS

TCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHD

FILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 625
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbRecd-Fc-
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

ICOSLecd
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDASTKGPSVFPLAPCSRSTS

ESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR

EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQP

REPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSL

GKGGGGSGGGGSGGGGSDTQEKEVRAMVGSDVELSCACPEGSRFDLNDV

YVYWQTSESKTVVTYHIPQNSSLENVDSRYRNRALMSPAGMLRGDFSLRL

FNVTPQDEQKFHCLVLSQSLGFQEVLSVEVTLHVAANFSVPVVSAPHSPSQ

DELTFTCTSINGYPRPNVYWINKTDNSLLDQALQNDTVFLNMRGLYDVVS

VLRIARTPSVNIGCCIENVLLQQNLTVGSQTGNDIGERDKITENPVSTGEKN

AATWS

SEQ ID NO: 626
DTQEKEVRAMVGSDVELSCACPEGSRFDLNDVYVYWQTSESKTVVTYHIP

ICOSLecd-Fc-
QNSSLENVDSRYRNRALMSPAGMLRGDFSLRLFNVTPQDEQKFHCLVLSQ

TGFbRecd
SLGFQEVLSVEVTLHVAANFSVPVVSAPHSPSQDELTFTCTSINGYPRPNVY

WINKTDNSLLDQALQNDTVFLNMRGLYDVVSVLRIARTPSVNIGCCIENVL

LQQNLTVGSQTGNDIGERDKITENPVSTGEKNAATWSASTKGPSVFPLAPC

SRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHITPAVLQSSGLYSLS

SVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNA

KTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISK

AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQK

SLSLSLGKGGGGSGGGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQ

LCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETV

CHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEY

NTSNPD

SEQ ID NO: 627
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbRecd-Fc-
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

LIGHTecd
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDASTKGPSVFPLAPCSRSTS

ESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR

EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQP

REPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSL

GKGGGGSGGGGSGGGGSDGPAGSWEQLIQERRSHEVNPAAHLTGANSSLT

GSGGPLLWETQLGLAFLRGLSYHDGALVVTKAGYYYIYSKVQLGGVGCPL

GLASTITHGLYKRTPRYPEELELLVSQQSPCGRATSSSRVWWDSSFLGGVV

HLEAGEKVVVRVLDERLVRLRDGTRSYFGAFMV

SEQ ID NO: 628
DGPAGSWEQLIQERRSHEVNPAAHLTGANSSLTGSGGPLLWETQLGLAFLR

LIGHTecd-Fc-
GLSYHDGALVVTKAGYYYIYSKVQLGGVGCPLGLASTITHGLYKRTPRYP

TGFbRecd
EELELLVSQQSPCGRATSSSRVWWDSSFLGGVVHLEAGEKVVVRVLDERL

VRLRDGTRSYFGAFMVASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDH

KPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVL

HQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLT

VDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGG

GSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSN

CSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCI

MKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 629
TIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSI

TGFbRecd-Fc-
TSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKE

OX40Lecd
KKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDASTKGPSVFPLAPCSRSTS

ESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR

EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQP

REPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSL

GKGGGGSGGGGSGGGGSQVSHRYPRIQSIKVQFTEYKKEKGFILTSQKEDEI

MKVQNNSVIINCDGFYLISLKGYFSQEVNISLHYQKDEEPLFQLKKVRSVNS

LMVASLTYKDKVYLNVTTDNTSLDDFHVNGGELILIHQNPGEFCVL

SEQ ID NO: 630
QVSHRYPRIQSIKVQFTEYKKEKGFILTSQKEDEIMKVQNNSVIINCDGFYLI

OX40Lecd-Fc-
SLKGYFSQEVNISLHYQKDEEPLFQLKKVRSVNSLMVASLTYKDKVYLNV

TGFbRecd
TTDNTSLDDFHVNGGELILIHQNPGEFCVLASTKGPSVFPLAPCSRSTSESTA

ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPK

PKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQ

VYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKG

GGGSGGGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRF

STCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYH

DFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 631
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFRecd-Fc-
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

41BBLecd
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKASTK

GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV

LQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPS

CPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYV

DGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL

PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE

ALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSACPWAVSGARASPGSAA

SPRLREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAG

VSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHL

QPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHT

EARARHAWQLTQGATVLGLFRVTPEIPAGLPSPRSE

SEQ ID NO: 632
ACPWAVSGARASPGSAASPRLREGPELSPDDPAGLLDLRQGMFAQLVAQN

41BBLecd-Fc-
VLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLEL

VEGFRecd
RRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQ

GRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLPSP

RSEASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG

VHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVES

KYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPE

VQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYK

CKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGF

YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVF

SCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSSDTGRPFVEMY

SEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIIS

NATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEK

LVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLST

LTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK

SEQ ID NO: 633
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFRecd-Fc-
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

CD30Lecd
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKASTK

GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV

LQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPS

CPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYV

DGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL

PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE

ALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSQRTDSIPNSPDNVPLKGG

NCSEDLLCILKRAPFKKSWAYLQVAKHLNKTKLSWNKDGILHGVRYQDG

NLVIQFPGLYFIICQLQFLVQCPNNSVDLKLELLINKHIKKQALVTVCESGM

QTKHVYQNLSQFLLDYLQVNTTISVNVDTFQYIDTSTFPLENVLSIFLYSNS

D

SEQ ID NO: 634
QRTDSIPNSPDNVPLKGGNCSEDLLCILKRAPFKKSWAYLQVAKHLNKTKL

CD30Lecd-Fc-
SWNKDGILHGVRYQDGNLVIQFPGLYFIICQLQFLVQCPNNSVDLKLELLIN

VEGFRecd
KHIKKQALVTVCESGMQTKHVYQNLSQFLLDYLQVNTTISVNVDTFQYIDT

STFPLENVLSIFLYSNSDASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPE

PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVD

HKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLT

VLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSR

LTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSG

GGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLI

PDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIID

VVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRD

LKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK

SEQ ID NO: 635
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFRecd-Fc-
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

CD40Lecd
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKASTK

GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHITPAV

LQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPS

CPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYV

DGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL

PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE

ALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSGDQNPQIAAHVISEASSKT

TSVLQWAEKGYYTMSNNLVTLENGKQLTVKRQGLYYIYAQVTFCSNREA

SSQAPFIASLCLKSPGRFERILLRAANTHSSAKPCGQQSIHLGGVFELQPGAS

VFVNVTDPSQVSHGTGFTSFGLLKL

SEQ ID NO: 636
GDQNPQIAAHVISEASSKTTSVLQWAEKGYYTMSNNLVTLENGKQLTVKR

CD40Lecd-Fc-
QGLYYIYAQVTFCSNREASSQAPFIASLCLKSPGRFERILLRAANTHSSAKPC

VEGFRecd
GQQSIHLGGVFELQPGASVFVNVTDPSQVSHGTGFTSFGLLKLASTKGPSVF

PLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG

LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPE

FLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEV

HNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEK

TISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNH

YTQKSLSLSLGKGGGGSGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRE

LVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCE

ATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELN

VGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGL

YTCAASSGLMTKKNSTFVRVHEK

SEQ ID NO: 637
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFRecd-Fc-
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

CD70ecd
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKASTK

GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHITPAV

LQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPS

CPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYV

DGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL

PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE

ALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSQRFAQAQQQLPLESLGW

DVAELQLNHTGPQQDPRLYWQGGPALGRSFLHGPELDKGQLRIHRDGIYM

VHIQVTLAICSSTTASRHHPTTLAVGICSPASRSISLLRLSFHQGCTIASQRLT

PLARGDTLCTNLTGTLLPSRNTDEIFFGVQWVRP

SEQ ID NO: 638
QRFAQAQQQLPLESLGWDVAELQLNHTGPQQDPRLYWQGGPALGRSFLH

CD70ecd-Fc -
GPELDKGQLRIHRDGIYMVHIQVTLAICSSTTASRHHPTTLAVGICSPASRSI

VEGFRecd
SLLRLSFHQGCTIASQRLTPLARGDTLCTNLTGTLLPSRNTDETFFGVQWVR

PASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVH

TFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKY

GPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQF

NWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCS

VMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSSDTGRPFVEMYSEI

PEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNA

TYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLV

LNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTI

DGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK

SEQ ID NO: 639
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFRecd-Fc-
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

GITRLecd
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKASTK

GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHITPAV

LQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPS

CPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYV

DGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL

PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE

ALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSQLETAKEPCMAKFGPLPS

KWQMASSEPPCVNKVSDWKLEILQNGLYLIYGQVAPNANYNDVAPFEVRL

YKNKDMIQTLTNKSKIQNVGGTYELHVGDTIDLIFNSEHQVLKNNTYWGII

LLANPQFIS

SEQ ID NO: 640
QLETAKEPCMAKFGPLPSKWQMASSEPPCVNKVSDWKLEILQNGLYLIYG

GITRLecd-Fc-
QVAPNANYNDVAPFEVRLYKNKDMIQTLTNKSKIQNVGGTYELHVGDTID

VEGFRecd
LIFNSEHQVLKNNTYWGIILLANPQFISASTKGPSVFPLAPCSRSTSESTAAL

GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS

TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQV

YTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGG

GGSGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVT

LKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYL

THRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKH

QHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKK

NSTFVRVHEK

SEQ ID NO: 641
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFRecd-Fc-
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

ICOSLecd
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKASTK

GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV

LQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPS

CPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYV

DGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL

PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE

ALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSDTQEKEVRAMVGSDVEL

SCACPEGSRFDLNDVYVYWQTSESKTVVTYHIPQNSSLENVDSRYRNRAL

MSPAGMLRGDFSLRLFNVTPQDEQKFHCLVLSQSLGFQEVLSVEVTLHVA

ANFSVPVVSAPHSPSQDELTFTCTSINGYPRPNVYWINKTDNSLLDQALQN

DTVFLNMRGLYDVVSVLRIARTPSVNIGCCIENVLLQQNLTVGSQTGNDIG

ERDKITENPVSTGEKNAATWS

SEQ ID NO: 642
DTQEKEVRAMVGSDVELSCACPEGSRFDLNDVYVYWQTSESKTVVTYHIP

ICOSLecd-Fc-
QNSSLENVDSRYRNRALMSPAGMLRGDFSLRLFNVTPQDEQKFHCLVLSQ

VEGFRecd
SLGFQEVLSVEVTLHVAANFSVPVVSAPHSPSQDELTFTCTSINGYPRPNVY

WINKTDNSLLDQALQNDTVFLNMRGLYDVVSVLRIARTPSVNIGCCIENVL

LQQNLTVGSQTGNDIGERDKITENPVSTGEKNAATWSASTKGPSVFPLAPC

SRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS

SVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNA

KTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISK

AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQK

SLSLSLGKGGGGSGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIP

CRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATV

NGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGID

FNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTC

AASSGLMTKKNSTFVRVHEK

SEQ ID NO: 643
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFRecd-Fc-
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

LIGHTecd
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKASTK

GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV

LQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPS

CPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYV

DGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL

PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE

ALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSDGPAGSWEQLIQERRSHE

VNPAAHLTGANSSLTGSGGPLLWETQLGLAFLRGLSYHDGALVVTKAGYY

YIYSKVQLGGVGCPLGLASTITHGLYKRTPRYPEELELLVSQQSPCGRATSS

SRVWWDSSFLGGVVHLEAGEKVVVRVLDERLVRLRDGTRSYFGAFMV

SEQ ID NO: 644
DGPAGSWEQLIQERRSHEVNPAAHLTGANSSLTGSGGPLLWETQLGLAFLR

LIGHTecd-Fc-
GLSYHDGALVVTKAGYYYIYSKVQLGGVGCPLGLASTITHGLYKRTPRYP

VEGFRecd
EELELLVSQQSPCGRATSSSRVWWDSSFLGGVVHLEAGEKVVVRVLDERL

VRLRDGTRSYFGAFMVASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP

VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDH

KPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVL

HQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLT

VDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGG

GSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPD

GKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVV

LSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLK

TQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK

SEQ ID NO: 645
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK

VEGFRecd-Fc -
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLS

OX40Lecd
PSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQ

SGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKASTK

GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV

LQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPS

CPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYV

DGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGL

PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE

ALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSQVSHRYPRIQSIKVQFTEY

KKEKGFILTSQKEDEIMKVQNNSVIINCDGFYLISLKGYFSQEVNISLHYQK

DEEPLFQLKKVRSVNSLMVASLTYKDKVYLNVTTDNTSLDDFHVNGGELI

LIHQNPGEFCVL

SEQ ID NO: 646
QVSHRYPRIQSIKVQFTEYKKEKGFILTSQKEDEIMKVQNNSVIINCDGFYLI

OX40Lecd-Fc-
SLKGYFSQEVNISLHYQKDEEPLFQLKKVRSVNSLMVASLTYKDKVYLNV

VEGFRecd
TTDNTSLDDFHVNGGELILIHQNPGEFCVLASTKGPSVFPLAPCSRSTSESTA

ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPK

PKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQF

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQ

VYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKG

GGGSGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITV

TLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNY

LTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSK

HQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTK

KNSTFVRVHEK

SEQ ID NO: 647
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1 HC
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

fused to 41BBL
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSACPWAVSGARASPGSAASPRLREGPELSPDDPAGLLDLRQG

MFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGV

YYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSE

ARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRV

TPEIPAGLPSPRSE

SEQ ID NO: 648
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1 HC
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

fused to CD30L
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSQRTDSIPNSPDNVPLKGGNCSEDLLCILKRAPFKKSWAYLQV

AKHLNKTKLSWNKDGILHGVRYQDGNLVIQFPGLYFIICQLQFLVQCPNNS

VDLKLELLINKHIKKQALVTVCESGMQTKHVYQNLSQFLLDYLQVNTTISV

NVDTFQYIDTSTFPLENVLSIFLYSNSD

SEQ ID NO: 649
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1 HC
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

fused to CD40L
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSGDQNPQIAAHVISEASSKTTSVLQWAEKGYYTMSNNLVTLE

NGKQLTVKRQGLYYIYAQVTFCSNREASSQAPFIASLCLKSPGRFERILLRA

ANTHSSAKPCGQQSIHLGGVFELQPGASVFVNVTDPSQVSHGTGFTSFGLL

KL

SEQ ID NO: 650
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1 HC
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

fused to CD70
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSQRFAQAQQQLPLESLGWDVAELQLNHTGPQQDPRLYWQGG

PALGRSFLHGPELDKGQLRIHRDGIYMVHIQVTLAICSSTTASRHHPTTLAV

GICSPASRSISLLRLSFHQGCTIASQRLTPLARGDTLCTNLTGTLLPSRNTDET

FFGVQWVRP

SEQ ID NO: 651
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1 HC
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

fused to GITRL
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSQLETAKEPCMAKFGPLPSKWQMASSEPPCVNKVSDWKLEIL

QNGLYLIYGQVAPNANYNDVAPFEVRLYKNKDMIQTLTNKSKIQNVGGTY

ELHVGDTIDLIFNSEHQVLKNNTYWGIILLANPQFIS

SEQ ID NO: 652
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1 HC
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

fused to ICOSL
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSDTQEKEVRAMVGSDVELSCACPEGSRFDLNDVYVYWQTSE

SKTVVTYHIPQNSSLENVDSRYRNRALMSPAGMLRGDFSLRLFNVTPQDEQ

KFHCLVLSQSLGFQEVLSVEVTLHVAANFSVPVVSAPHSPSQDELTFTCTSI

NGYPRPNVYWINKTDNSLLDQALQNDTVFLNMRGLYDVVSVLRIARTPSV

NIGCCIENVLLQQNLTVGSQTGNDIGERDKITENPVSTGEKNAATWS

SEQ ID NO: 653
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1 HC
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

fused to IL12
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSIWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTL

DQSSEVLGSGKTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWS

TDILKDQKEPKNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDP

QGVTCGAATLSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAV

HKLKYENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTWSTPHS

YFSLTFCVQVQGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSS

WSEWASVPCSGGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQNLLR

AVSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLN

SRETSFITNGSCLASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAKLLMDP

KRQIFLDQNMLAVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHA

FRIRAVTIDRVMSYLNAS

SEQ ID NO: 654
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1 HC
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

fused to IL15
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSNWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMK

CFLLELQVISLESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEK

NIKEFLQSFVHIVQMFINTS

SEQ ID NO: 655
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1 HC
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

fused to LIGHT
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSDGPAGSWEQLIQERRSHEVNPAAHLTGANSSLTGSGGPLLW

ETQLGLAFLRGLSYHDGALVVTKAGYYYIYSKVQLGGVGCPLGLASTITH

GLYKRTPRYPEELELLVSQQSPCGRATSSSRVWWDSSFLGGVVHLEAGEK

VVVRVLDERLVRLRDGTRSYFGAFMV

SEQ ID NO: 656
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVA

anti-PDL1 HC
WISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARR

fused to OX40L
HWPGGFDYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

ECD
YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC

NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL

MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSG

GGGSGGGGSQVSHRYPRIQSIKVQFTEYKKEKGFILTSQKEDEIMKVQNNS

VIINCDGFYLISLKGYFSQEVNISLHYQKDEEPLFQLKKVRSVNSLMVASLT

YKDKVYLNVTTDNTSLDDFHVNGGELILIHQNPGEFCVL

SEQ ID NO: 657
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-PDL1 LC
SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTK

fused to 41BBL
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSACPWAVSGARASPGSAASPRLREGPE

LSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLS

YKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAG

AAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHA

WQLTQGATVLGLFRVTPEIPAGLPSPRSE

SEQ ID NO: 658
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-PDL1 LC
SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTK

fused to CD30L
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSQRTDSIPNSPDNVPLKGGNCSEDLLCI

LKRAPFKKSWAYLQVAKHLNKTKLSWNKDGILHGVRYQDGNLVIQFPGL

YFIICQLQFLVQCPNNSVDLKLELLINKHIKKQALVTVCESGMQTKHVYQN

LSQFLLDYLQVNTTISVNVDTFQYIDTSTFPLENVLSIFLYSNSD

SEQ ID NO: 659
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-PDL1 LC
SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTK

fused to CD40L
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSGDQNPQIAAHVISEASSKTTSVLQWA

EKGYYTMSNNLVTLENGKQLTVKRQGLYYIYAQVTFCSNREASSQAPFIAS

LCLKSPGRFERILLRAANTHSSAKPCGQQSIHLGGVFELQPGASVFVNVTDP

SQVSHGTGFTSFGLLKL

SEQ ID NO: 660
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-PDL1 LC
SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTK

fused to CD70
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSQRFAQAQQQLPLESLGWDVAELQLN

HTGPQQDPRLYWQGGPALGRSFLHGPELDKGQLRIHRDGIYMVHIQVTLAI

CSSTTASRHHPTTLAVGICSPASRSISLLRLSFHQGCTIASQRLTPLARGDTLC

TNLTGTLLPSRNTDETFFGVQWVRP

SEQ ID NO: 661
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-PDL1 LC
SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTK

fused to GITRL
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSQLETAKEPCMAKFGPLPSKWQMASSE

PPCVNKVSDWKLEILQNGLYLIYGQVAPNANYNDVAPFEVRLYKNKDMIQ

TLTNKSKIQNVGGTYELHVGDTIDLIFNSEHQVLKNNTYWGIILLANPQFIS

SEQ ID NO: 662
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-PDL1 LC
SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTK

fused to ICOSL
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSDTQEKEVRAMVGSDVELSCACPEGSR

FDLNDVYVYWQTSESKTVVTYHIPQNSSLENVDSRYRNRALMSPAGMLRG

DFSLRLFNVTPQDEQKFHCLVLSQSLGFQEVLSVEVTLHVAANFSVPVVSA

PHSPSQDELTFTCTSINGYPRPNVYWINKTDNSLLDQALQNDTVFLNMRGL

YDVVSVLRIARTPSVNIGCCIENVLLQQNLTVGSQTGNDIGERDKITENPVS

TGEKNAATWS

SEQ ID NO: 663
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-PDL1 LC
SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTK

fused to IL12
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSIWELKKDVYVVELDWYPDAPGEMVV

LTCDTPEEDGITWTLDQSSEVLGSGKTLTIQVKEFGDAGQYTCHKGGEVLS

HSLLLLHKKEDGIWSTDILKDQKEPKNKTFLRCEAKNYSGRFTCWWLTTIS

TDLTFSVKSSRGSSDPQGVTCGAATLSAERVRGDNKEYEYSVECQEDSACP

AAEESLPIEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQV

EVSWEYPDTWSTPHSYFSLTFCVQVQGKSKREKKDRVFTDKTSATVICRK

NASISVRAQDRYYSSSWSEWASVPCSGGGGSGGGGSGGGGSRNLPVATPD

PGMFPCLHHSQNLLRAVSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTV

EACLPLELTKNESCLNSRETSFITNGSCLASRKTSFMMALCLSSIYEDLKMY

QVEFKTMNAKLLMDPKRQIFLDQNMLAV1DELMQALNFNSETVPQKSSLE

EPDFYKTKIKLCILLHAFRIRAVTIDRVMSYLNAS

SEQ ID NO: 664
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-PDL1 LC
SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTK

fused to IL15
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSNWVNVISDLKKIEDLIQSMHIDATLYT

ESDVHPSCKVTAMKCFLLELQVISLESGDASIHDTVENLIILANNSLSSNGN

VTESGCKECEELEEKNIKEFLQSFVHIVQMFINTS

SEQ ID NO: 665
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-PDL1 LC
SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTK

fused to LIGHT
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSDGPAGSWEQLIQERRSHEVNPAAHLT

GANSSLTGSGGPLLWETQLGLAFLRGLSYHDGALVVTKAGYYYIYSKVQL

GGVGCPLGLASTITHGLYKRTPRYPEELELLVSQQSPCGRATSSSRVWWDS

SFLGGVVHLEAGEKVVVRVLDERLVRLRDGTRSYFGAFMV

SEQ ID NO: 666
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSA

anti-PDL1 LC
SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTK

fused to OX40L
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSQVSHRYPRIQSIKVQFTEYKKEKGFIL

TSQKEDEIMKVQNNSVIINCDGFYLISLKGYFSQEVNISLHYQKDEEPLFQL

KKVRSVNSLMVASLTYKDKVYLNVTTDNTSLDDFHVNGGELILIHQNPGE

FCVL

SEQ ID NO: 667
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR HC
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to 41BBL
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFYAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSACPWAVSGARASPGSAASPRLREGPELSPDDPAGLLDLRQGMF

AQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYY

VFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEAR

NSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPE

IPAGLPSPRSE

SEQ ID NO: 668
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR HC
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to CD30L
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFYAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSQRTDSIPNSPDNVPLKGGNCSEDLLCILKRAPFKKSWAYLQVAK

HLNKTKLSWNKDGILHGVRYQDGNLVIQFPGLYFIICQLQFLVQCPNNSVD

LKLELLINKHIKKQALVTVCESGMQTKHVYQNLSQFLLDYLQVNTTISVNV

DTFQYIDTSTFPLENVLSIFLYSNSD

SEQ ID NO: 669
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR HC
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to CD40L
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFYAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSGDQNPQIAAHVISEASSKTTSVLQWAEKGYYTMSNNLVTLENG

KQLTVKRQGLYYIYAQVTFCSNREASSQAPFIASLCLKSPGRFERILLRAAN

THSSAKPCGQQSIHLGGVFELQPGASVFVNVTDPSQVSHGTGFTSFGLLKL

SEQ ID NO: 670
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR HC
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to CD70
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFYAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSQRFAQAQQQLPLESLGWDVAELQLNHTGPQQDPRLYWQGGPA

LGRSFLHGPELDKGQLRIHRDGIYMVHIQVTLAICSSTTASRHHPTTLAVGI

CSPASRSISLLRLSFHQGCTIASQRLTPLARGDTLCTNLTGTLLPSRNTDETFF

GVQWVRP

SEQ ID NO: 671
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR HC
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to GITRL
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFYAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSQLETAKEPCMAKFGPLPSKWQMASSEPPCVNKVSDWKLEILQN

GLYLIYGQVAPNANYNDVAPFEVRLYKNKDMIQTLTNKSKIQNVGGTYEL

HVGDTIDLIFNSEHQVLKNNTYWGIILLANPQFIS

SEQ ID NO: 672
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR HC
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to ICOSL
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFYAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSDTQEKEVRAMVGSDVELSCACPEGSRFDLNDVYVYWQTSESK

TVVTYHIPQNSSLENVDSRYRNRALMSPAGMLRGDFSLRLFNVTPQDEQKF

HCLVLSQSLGFQEVLSVEVTLHVAANFSVPVVSAPHSPSQDELTFTCTSING

YPRPNVYWINKTDNSLLDQALQNDTVFLNMRGLYDVVSVLRIARTPSVNI

GCCIENVLLQQNLTVGSQTGNDIGERDKITENPVSTGEKNAATWS

SEQ ID NO: 673
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR HC
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to IL12
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHIFYAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSIWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQ

SSEVLGSGKTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTD

ILKDQKEPKNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQG

VTCGAATLSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHK

LKYENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTWSTPHSYF

SLTFCVQVQGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWS

EWASVPCSGGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQNLLRAVS

NMLQKARQTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRE

TSFITNGSCLASRKTSFMNIALCLSSIYEDLKMYQVEFKTMNAKLLMDPKR

QIFLDQNMLAVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRI

RAVTIDRVMSYLNAS

SEQ ID NO: 674
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR HC
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to IL15
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSNWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFL

LELQVISLESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIK

EFLQSFVHIVQMFINTS

SEQ ID NO: 675
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR HC
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to LIGHT
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSDGPAGSWEQLIQERRSHEVNPAAHLTGANSSLTGSGGPLLWET

QLGLAFLRGLSYHDGALVVTKAGYYYIYSKVQLGGVGCPLGLASTITHGL

YKRTPRYPEELELLVSQQSPCGRATSSSRVWWDSSFLGGVVHLEAGEKVV

VRVLDERLVRLRDGTRSYFGAFMV

SEQ ID NO: 676
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVI

anti-EGFR HC
WSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYY

fused to OX40L
DYEFAYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN

HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSQVSHRYPRIQSIKVQFTEYKKEKGFILTSQKEDEIMKVQNNSVII

NCDGFYLISLKGYFSQEVNISLHYQKDEEPLFQLKKVRSVNSLMVASLTYK

DKVYLNVTTDNTSLDDFHVNGGELILIHQNPGEFCVL

SEQ ID NO: 677
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES

anti-EGFR LC
ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK

fused to 41BBL
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

ECD
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGECGGGGSGGGGSGGGGSACPWAVSGARASPGSAASPRLREGPELSPD

DPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKED

TKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAAL

ALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLT

QGATVLGLFRVTPEIPAGLPSPRSE

SEQ ID NO: 678
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES

anti-EGFR LC
ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK

fused to CD30L
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

ECD
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGECGGGGSGGGGSGGGGSQRTDSIPNSPDNVPLKGGNCSEDLLCILKRA

PFKKSWAYLQVAKHLNKTKLSWNKDGILHGVRYQDGNLVIQFPGLYFIIC

QLQFLVQCPNNSVDLKLELLINKHIKKQALVTVCESGMQTKHVYQNLSQF

LLDYLQVNTTISVNVDTFQYIDTSTFPLENVLSIFLYSNSD

SEQ ID NO: 679
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES

anti-EGFR LC
ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK

fused to CD40L
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

ECD
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGECGGGGSGGGGSGGGGSGDQNPQIAAHVISEASSKTTSVLQWAEKGY

YTMSNNLVTLENGKQLTVKRQGLYYIYAQVTFCSNREASSQAPFIASLCLK

SPGRFERILLRAANTHSSAKPCGQQSIHLGGVFELQPGASVFVNVTDPSQVS

HGTGFTSFGLLKL

SEQ ID NO: 680
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES

anti-EGFR LC
ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK

fused to CD70
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

ECD
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGECGGGGSGGGGSGGGGSQRFAQAQQQLPLESLGWDVAELQLNHTGP

QQDPRLYWQGGPALGRSFLHGPELDKGQLRIHRDGIYMVHIQVTLAICSST

TASRHHPTTLAVGICSPASRSISLLRLSFHQGCTIASQRLTPLARGDTLCTNL

TGTLLPSRNTDETFFGVQWVRP

SEQ ID NO: 681
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES

anti-EGFR LC
ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK

fused to GITRL
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

ECD
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGECGGGGSGGGGSGGGGSQLETAKEPCMAKFGPLPSKWQMASSEPPC

VNKVSDWKLEILQNGLYLIYGQVAPNANYNDVAPFEVRLYKNKDMIQTLT

NKSKIQNVGGTYELHVGDTIDLIFNSEHQVLKNNTYWGIILLANPQFIS

SEQ ID NO: 682
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES

anti-EGFR LC
ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK

fused to ICOSL
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

ECD
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGECGGGGSGGGGSGGGGSDTQEKEVRAMVGSDVELSCACPEGSRFDL

NDVYVYWQTSESKTVVTYHIPQNSSLENVDSRYRNRALMSPAGMLRGDFS

LRLFNVTPQDEQKFHCLVLSQSLGFQEVLSVEVTLHVAANFSVPVVSAPHS

PSQDELTFTCTSINGYPRPNVYWINKTDNSLLDQALQNDTVFLNMRGLYDV

VSVLRIARTPSVNIGCCIENVLLQQNLTVGSQTGNDIGERDKITENPVSTGEK

NAATWS

SEQ ID NO: 683
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES

anti-EGFR LC
ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK

fused to IL12
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

ECD
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGECGGGGSGGGGSGGGGSIWELKKDVYVVELDWYPDAPGEMVVLTC

DTPEEDGITWTLDQSSEVLGSGKTLTIQVKEFGDAGQYTCHKGGEVLSHSL

LLLHKKEDGIWSTDILKDQKEPKNKTFLRCEAKNYSGRFTCWWLTTISTDL

TFSVKSSRGSSDPQGVTCGAATLSAERVRGDNKEYEYSVECQEDSACPAAE

ESLPIEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQVEVS

WEYPDTWSTPHSYFSLTFCVQVQGKSKREKKDRVFTDKTSATVICRKNASI

SVRAQDRYYSSSWSEWASVPCSGGGGSGGGGSGGGGSRNLPVATPDPGM

FPCLHHSQNLLRAVSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTVEACL

PLELTKNESCLNSRETSFITNGSCLASRKTSFMNIALCLSSIYEDLKMYQVEF

KTMNAKLLMDPKRQIFLDQNMLAVIDELMQALNFNSETVPQKSSLEEPDF

YKTKIKLCILLHAFRIRAVTIDRVMSYLNAS

SEQ ID NO: 684
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES

anti-EGFR LC
ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK

fused to IL15
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

ECD
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGECGGGGSGGGGSGGGGSNWVNVISDLKKIEDLIQSMHIDATLYTESD

VHPSCKVTAMKCFLLELQVISLESGDASIHDTVENLIILANNSLSSNGNVTES

GCKECEELEEKNIKEFLQSFVHIVQMFINTS

SEQ ID NO: 685
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES

anti-EGFR LC
ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK

fused to LIGHT
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

ECD
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGECGGGGSGGGGSGGGGSDGPAGSWEQLIQERRSHEVNPAAHLTGANS

SLTGSGGPLLWETQLGLAFLRGLSYHDGALVVTKAGYYYIYSKVQLGGVG

CPLGLASTITHGLYKRTPRYPEELELLVSQQSPCGRATSSSRVWWDSSFLGG

VVHLEAGEKVVVRVLDERLVRLRDGTRSYFGAFMV

SEQ ID NO: 686
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASES

anti-EGFR LC
ISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK

fused to OX40L
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN

ECD
SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF

NRGECGGGGSGGGGSGGGGSQVSHRYPRIQSIKVQFTEYKKEKGFILTSQK

EDEIMKVQNNSVIINCDGFYLISLKGYFSQEVNISLHYQKDEEPLFQLKKVR

SVNSLMVASLTYKDKVYLNVTTDNTSLDDFHVNGGELILIHQNPGEFCVL

SEQ ID NO: 687
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to 41BBL
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

STKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSACPWAVSGARASPGSAASPRLREGPELSPDDPAGLLDLRQGMFAQL

VAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFF

QLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSA

FGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPA

GLPSPRSE

SEQ ID NO: 688
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to CD30L
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSQRTDSIPNSPDNVPLKGGNCSEDLLCILKRAPFKKSWAYLQVAKHLN

KTKLSWNKDGILHGVRYQDGNLVIQFPGLYFIICQLQFLVQCPNNSVDLKL

ELLINKHIKKQALVTVCESGMQTKHVYQNLSQFLLDYLQVNTTISVNVDTF

QYIDTSTFPLENVLSIFLYSNSD

SEQ ID NO: 689
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to CD40L
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSGDQNPQIAAHVISEASSKITSVLQWAEKGYYTMSNNLVTLENGKQL

TVKRQGLYYIYAQVTFCSNREASSQAPFIASLCLKSPGRFERILLRAANTHSS

AKPCGQQSIHLGGVFELQPGASVFVNVTDPSQVSHGTGFTSFGLLKL

SEQ ID NO: 690
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to CD70
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSQRFAQAQQQLPLESLGWDVAELQLNHTGPQQDPRLYWQGGPALGR

SFLHGPELDKGQLRIHRDGIYMVHIQVTLAICSSTTASRHHPTTLAVGICSPA

SRSISLLRLSFHQGCTIASQRLTPLARGDTLCTNLTGTLLPSRNTDETFFGVQ

WVRP

SEQ ID NO: 691
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to GITRL
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSQLETAKEPCMAKFGPLPSKWQMASSEPPCVNKVSDWKLEILQNGLY

LIYGQVAPNANYNDVAPFEVRLYKNKDMIQTLTNKSKIQNVGGTYELHVG

DTIDLIFNSEHQVLKNNTYWGIILLANPQFIS

SEQ ID NO: 692
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to ICOSL
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSDTQEKEVRAMVGSDVELSCACPEGSRFDLNDVYVYWQTSESKTVV

TYHIPQNSSLENVDSRYRNRALMSPAGMLRGDFSLRLFNVTPQDEQKFHCL

VLSQSLGFQEVLSVEVTLHVAANFSVPVVSAPHSPSQDELTFTCTSINGYPR

PNVYWINKTDNSLLDQALQNDTVFLNMRGLYDVVSVLRIARTPSVNIGCCI

ENVLLQQNLTVGSQTGNDIGERDKITENPVSTGEKNAATWS

SEQ ID NO: 693
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to IL12
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSIWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEV

LGSGKTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKD

QKEPKNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQGVTC

GAATLSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHKLKY

ENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTF

CVQVQGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEWA

SVPCSGGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQNLLRAVSNML

QKARQTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFI

TNGSCLASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFL

DQNMLAVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAV

TIDRVMSYLNAS

SEQ ID NO: 694
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to IL15
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSNWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLEL

QVISLESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFL

QSFVHIVQMFINTS

SEQ ID NO: 695
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to LIGHT
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHIFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSDGPAGSWEQLIQERRSHEVNPAAHLTGANSSLTGSGGPLLWETQLG

LAFLRGLSYHDGALVVTKAGYYYIYSKVQLGGVGCPLGLASTITHGLYKR

TPRYPEELELLVSQQSPCGRATSSSRVWWDSSFLGGVVHLEAGEKVVVRV

LDERLVRLRDGTRSYFGAFMV

SEQ ID NO: 696
QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGISWVRQAPGQGLEWMG

anti-IL17R HC
WISTYSGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARR

fused to OX40L
QLYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP

ECD
EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNV

DHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT

VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSG

GGGSQVSHRYPRIQSIKVQFTEYKKEKGFILTSQKEDEIMKVQNNSVIINCD

GFYLISLKGYFSQEVNISLHYQKDEEPLFQLKKVRSVNSLMVASLTYKDKV

YLNVTTDNTSLDDFHVNGGELILIHQNPGEFCVL

SEQ ID NO: 697
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWFQQKPGQAPRPLIYDAS

anti-IL17R LC
TRATGVPARFSGSGSGTDFTLTISSLQSEDFAVYYCQQYDNWPLTFGGGTK

fused to 41BBL
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSACPWAVSGARASPGSAASPRLREGPE

LSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLS

YKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAG

AAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHA

WQLTQGATVLGLFRVTPEIPAGLPSPRSE

SEQ ID NO: 698
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWFQQKPGQAPRPLIYDAS

anti-IL17R LC
TRATGVPARFSGSGSGTDFTLTISSLQSEDFAVYYCQQYDNWPLTFGGGTK

fused to CD30L
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSQRTDSIPNSPDNVPLKGGNCSEDLLCI

LKRAPFKKSWAYLQVAKHLNKTKLSWNKDGILHGVRYQDGNLVIQFPGL

YFIICQLQFLVQCPNNSVDLKLELLINKHIKKQALVTVCESGMQTKHVYQN

LSQFLLDYLQVNTTISVNVDTFQYIDTSTFPLENVLSIFLYSNSD

SEQ ID NO: 699
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWFQQKPGQAPRPLIYDAS

anti-IL17R LC
TRATGVPARFSGSGSGTDFTLTISSLQSEDFAVYYCQQYDNWPLTFGGGTK

fused to CD40L
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSGDQNPQIAAHVISEASSKTTSVLQWA

EKGYYTMSNNLVTLENGKQLTVKRQGLYYIYAQVTFCSNREASSQAPFIAS

LCLKSPGRFERILLRAANTHSSAKPCGQQSIHLGGVFELQPGASVFVNVTDP

SQVSHGTGFTSFGLLKL

SEQ ID NO: 700
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWFQQKPGQAPRPLIYDAS

anti-IL17R LC
TRATGVPARFSGSGSGTDFTLTISSLQSEDFAVYYCQQYDNWPLTFGGGTK

fused to CD70
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSQRFAQAQQQLPLESLGWDVAELQLN

HTGPQQDPRLYWQGGPALGRSFLHGPELDKGQLRIHRDGIYMVHIQVTLAI

CSSTTASRHHPTTLAVGICSPASRSISLLRLSFHQGCTIASQRLTPLARGDTLC

TNLTGTLLPSRNTDEITTGVQWVRP

SEQ ID NO: 701
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWFQQKPGQAPRPLIYDAS

anti-IL17R LC
TRATGVPARFSGSGSGTDFTLTISSLQSEDFAVYYCQQYDNWPLTFGGGTK

fused to GITRL
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSQLETAKEPCMAKFGPLPSKWQMASSE

PPCVNKVSDWKLEILQNGLYLIYGQVAPNANYNDVAPFEVRLYKNKDMIQ

TLTNKSKIQNVGGTYELHVGDTIDLIFNSEHQVLKNNTYWGIILLANPQFIS

SEQ ID NO: 702
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWFQQKPGQAPRPLIYDAS

anti-IL17R LC
TRATGVPARFSGSGSGTDFTLTISSLQSEDFAVYYCQQYDNWPLTFGGGTK

fused to ICOSL
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSDTQEKEVRAMVGSDVELSCACPEGSR

FDLNDVYVYWQTSESKTVVTYHIPQNSSLENVDSRYRNRALMSPAGMLRG

DFSLRLFNVTPQDEQKFHCLVLSQSLGFQEVLSVEVTLHVAANFSVPVVSA

PHSPSQDELTFTCTSINGYPRPNVYWINKTDNSLLDQALQNDTVFLNMRGL

YDVVSVLRIARTPSVNIGCCIENVLLQQNLTVGSQTGNDIGERDKITENPVS

TGEKNAATWS

SEQ ID NO: 703
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWFQQKPGQAPRPLIYDAS

anti- IL17R LC
TRATGVPARFSGSGSGTDFTLTISSLQSEDFAVYYCQQYDNWPLTFGGGTK

fused to IL12
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSIWELKKDVYVVELDWYPDAPGEMVV

LTCDTPEEDGITWTLDQSSEVLGSGKTLTIQVKEFGDAGQYTCHKGGEVLS

HSLLLLHKKEDGIWSTDILKDQKEPKNKIFLRCEAKNYSGRFTCWWLTTIS

TDLTFSVKSSRGSSDPQGVTCGAATLSAERVRGDNKEYEYSVECQEDSACP

AAEESLPIEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQV

EVSWEYPDTWSTPHSYFSLTFCVQVQGKSKREKKDRVFTDKTSATVICRK

NASISVRAQDRYYSSSWSEWASVPCSGGGGSGGGGSGGGGSRNLPVATPD

PGMFPCLHHSQNLLRAVSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTV

EACLPLELTKNESCLNSRETSFITNGSCLASRKTSFMMALCLSSIYEDLKMY

QVEFKTMNAKLLMDPKRQIFLDQNMLAVIDELMQALNFNSETVPQKSSLE

EPDFYKTKIKLCILLHAFRIRAVTIDRVMSYLNAS

SEQ ID NO: 704
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWFQQKPGQAPRPLIYDAS

anti-IL17R LC
TRATGVPARFSGSGSGTDFTLTISSLQSEDFAVYYCQQYDNWPLTFGGGTK

fused to IL15
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSNWVNVISDLKKIEDLIQSMHIDATLYT

ESDVHPSCKVTAMKCFLLELQVISLESGDASIHDTVENLIILANNSLSSNGN

VTESGCKECEELEEKNIKEFLQSFVHIVQMFINTS

SEQ ID NO: 705
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWFQQKPGQAPRPLIYDAS

anti-IL17R LC
TRATGVPARFSGSGSGTDFTLTISSLQSEDFAVYYCQQYDNWPLTFGGGTK

fused to LIGHT
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSDGPAGSWEQLIQERRSHEVNPAAHLT

GANSSLTGSGGPLLWETQLGLAFLRGLSYHDGALVVTKAGYYYIYSKVQL

GGVGCPLGLASTITHGLYKRTPRYPEELELLVSQQSPCGRATSSSRVWWDS

SFLGGVVHLEAGEKVVVRVLDERLVRLRDGTRSYFGAFMV

SEQ ID NO: 706
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWFQQKPGQAPRPLIYDAS

anti-IL17R LC
TRATGVPARFSGSGSGTDFTLTISSLQSEDFAVYYCQQYDNWPLTFGGGTK

fused to OX40L
VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

ECD
QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGECGGGGSGGGGSGGGGSQVSHRYPRIQSIKVQFTEYKKEKGFIL

TSQKEDEIMKVQNNSVIINCDGFYLISLKGYFSQEVNISLHYQKDEEPLFQL

KKVRSVNSLMVASLTYKDKVYLNVTTDNTSLDDFHVNGGELILIHQNPGE

FCVL

SEQ ID NO: 707
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anti-VEGF HC
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

fused to 41BBL
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

ECD
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSACPWAVSGARASPGSAASPRLREGPELSPDDPAGL

LDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELV

VAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVD

LPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATV

LGLFRVTPEIPAGLPSPRSE

SEQ ID NO: 708
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anti-VEGF HC
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

fused to CD30L
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

ECD
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSQRTDSIPNSPDNVPLKGGNCSEDLLCILKRAPFKKS

WAYLQVAKHLNKTKLSWNKDGILHGVRYQDGNLVIQFPGLYFIICQLQFL

VQCPNNSVDLKLELLINKHIKKQALVTVCESGMQTKHVYQNLSQFLLDYL

QVNTTISVNVDTFQYIDTSTFPLENVLSIFLYSNSD

SEQ ID NO: 709
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anti-VEGF HC
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

fused to CD40L
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

ECD
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSGDQNPQIAAHVISEASSKTTSVLQWAEKGYYTMSN

NLVTLENGKQLTVKRQGLYYIYAQVTFCSNREASSQAPFIASLCLKSPGRFE

RILLRAANTHSSAKPCGQQSIHLGGVFELQPGASVFVNVTDPSQVSHGTGFT

SFGLLKL

SEQ ID NO: 710
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anti-VEGF HC
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

fused to CD70
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

ECD
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSQRFAQAQQQLPLESLGWDVAELQLNHTGPQQDPR

LYWQGGPALGRSFLHGPELDKGQLRIHRDGIYMVHIQVTLAICSSTTASRH

HPTTLAVGICSPASRSISLLRLSFHQGCTIASQRLTPLARGDTLCTNLTGTLLP

SRNTDETFFGVQWVRP

SEQ ID NO: 711
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anti-VEGF HC
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

fused to GITRL
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

ECD
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSQLETAKEPCMAKFGPLPSKWQMASSEPPCVNKVS

DWKLEILQNGLYLIYGQVAPNANYNDVAPFEVRLYKNKDMIQTLTNKSKI

QNVGGTYELHVGDTIDLIFNSEHQVLKNNTYWGIILLANPQFIS

SEQ ID NO: 712
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anfi-VEGF HC
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

fused to ICOSL
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

ECD
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKFIPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSDTQEKEVRAMVGSDVELSCACPEGSRFDLNDVYV

YWQTSESKTVVTYHIPQNSSLENVDSRYRNRALMSPAGMLRGDFSLRLFN

VTPQDEQKFHCLVLSQSLGFQEVLSVEVTLHVAANFSVPVVSAPHSPSQDE

LTFTCTSINGYPRPNVYWINKTDNSLLDQALQNDTVFLNMRGLYDVVSVL

RIARTPSVNIGCCIENVLLQQNLTVGSQTGNDIGERDKITENPVSTGEKNAA

TWS

EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

SEQ ID NO: 713
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

anti-VEGF HC
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

fused to IL12
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

ECD
QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSIWELKKDVYVVELDWYPDAPGEMVVLTCDTPEED

GITWTLDQSSEVLGSGKTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKK

EDGIWSTDILKDQKEPKNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSS

RGSSDPQGVTCGAATLSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEV

MVDAVHKLKYENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDT

WSTPHSYFSLTFCVQVQGKSKREKKDRVFTDKTSATVICRKNASISVRAQD

RYYSSSWSEWASVPCSGGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHS

QNLLRAVSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKN

ESCLNSRETSFITNGSCLASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAK

LLMDPKRQIFLDQNMLAVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKL

CILLHAFRIRAVTIDRVMSYLNAS

SEQ ID NO: 714
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anti-VEGF HC
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

fused to IL15
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

ECD
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSNWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCK

VTAMKCFLLELQVISLESGDASIHDTVENLIILANNSLSSNGNVTESGCKECE

ELEEKNIKEFLQSFVHIVQMFINTS

SEQ ID NO: 715
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anti-VEGF HC
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

fused to LIGHT
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

ECD
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSDGPAGSWEQLIQERRSHEVNPAAHLTGANSSLTGS

GGPLLWETQLGLAFLRGLSYHDGALVVTKAGYYYIYSKVQLGGVGCPLGL

ASTITHGLYKRTPRYPEELELLVSQQSPCGRATSSSRVWWDSSFLGGVVHL

EAGEKVVVRVLDERLVRLRDGTRSYFGAFMV

SEQ ID NO: 716
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVG

anti-VEGF HC
WINTYTGEPTYAADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKY

fused to OX40L
PHYYGSSHWYFDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG

ECD
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

QTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSQVSHRYPRIQSIKVQFTEYKKEKGFILTSQKEDEIM

KVQNNSVIINCDGFYLISLKGYFSQEVNISLHYQKDEEPLFQLKKVRSVNSL

MVASLTYKDKVYLNVTTDNTSLDDFHVNGGELILIHQNPGEFCVL

SEQ ID NO: 717
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTS

anti-VEGF LC
SLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKV

fused to 41BBL
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSACPWAVSGARASPGSAASPRLREGPEL

SPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSY

KEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGA

AALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAW

QLTQGATVLGLFRVTPEIPAGLPSPRSE

SEQ ID NO: 718
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTS

anti-VEGF LC
SLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKV

fused to CD30L
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSQRTDSIPNSPDNVPLKGGNCSEDLLCIL

KRAPFKKSWAYLQVAKHLNKTKLSWNKDGILHGVRYQDGNLVIQFPGLY

FIICQLQFLVQCPNNSVDLKLELLINKHIKKQALVTVCESGMQTKHVYQNL

SQFLLDYLQVNTTISVNVDTFQYIDTSTFPLENVLSIFLYSNSD

SEQ ID NO: 719
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTS

anti-VEGF LC
SLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKV

fused to CD40L
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSGDQNPQIAAHVISEASSKTTSVLQWAE

KGYYTMSNNLVTLENGKQLTVKRQGLYYIYAQVTFCSNREASSQAPFIASL

CLKSPGRFERILLRAANTHSSAKPCGQQSIHLGGVFELQPGASVFVNVTDPS

QVSHGTGFTSFGLLKL

SEQ ID NO: 720
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTS

anti-VEGF LC
SLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKV

fused to CD70
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSQRFAQAQQQLPLESLGWDVAELQLNH

TGPQQDPRLYWQGGPALGRSFLHGPELDKGQLRIHRDGIYMVHIQVTLAIC

SSTTASRHHPTTLAVGICSPASRSISLLRLSFHQGCTIASQRLTPLARGDTLCT

NLTGTLLPSRNTDETFFGVQWVRP

SEQ ID NO: 721
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTS

anti-VEGF LC
SLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKV

fused to GITRL
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSQLETAKEPCMAKFGPLPSKWQMASSEP

PCVNKVSDWKLEILQNGLYLIYGQVAPNANYNDVAPFEVRLYKNKDMIQT

LTNKSKIQNVGGTYELHVGDTIDLIFNSEHQVLKNNTYWGIILLANPQFIS

SEQ ID NO: 722
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTS

anti-VEGF LC
SLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKV

fused to ICOSL
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSDTQEKEVRAMVGSDVELSCACPEGSRF

DLNDVYVYWQTSESKTVVTYHIPQNSSLENVDSRYRNRALMSPAGMLRG

DFSLRLFNVTPQDEQKFHCLVLSQSLGFQEVLSVEVTLHVAANFSVPVVSA

PHSPSQDELTFTCTSINGYPRPNVYWINKTDNSLLDQALQNDTVFLNMRGL

YDVVSVLRIARTPSVNIGCCIENVLLQQNLTVGSQTGNDIGERDKITENPVS

TGEKNAATWS

SEQ ID NO: 723
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTS

anti-VEGF LC
SLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKV

fused to IL12
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSIWELKKDVYVVELDWYPDAPGEMVVL

TCDTPEEDGITWTLDQSSEVLGSGKTLTIQVKEFGDAGQYTCHKGGEVLSH

SLLLLHKKEDGIWSTDILKDQKEPKNKITLRCEAKNYSGRFTCWWLTTIST

DLTFSVKSSRGSSDPQGVTCGAATLSAERVRGDNKEYEYSVECQEDSACPA

AEESLPIEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQVE

VSWEYPDTWSTPHSYFSLTFCVQVQGKSKREKKDRVFTDKTSATVICRKN

ASISVRAQDRYYSSSWSEWASVPCSGGGGSGGGGSGGGGSRNLPVATPDP

GMFPCLHHSQNLLRAVSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTVE

ACLPLELTKNESCLNSRETSFITNGSCLASRKTSFMMALCLSSIYEDLKMYQ

VEFKTMNAKLLMDPKRQIFLDQNMLAVIDELMQALNFNSETVPQKSSLEEP

DFYKTKIKLCILLHAFRIRAVTIDRVMSYLNAS

SEQ ID NO: 724
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTS

anti-VEGF LC
SLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKV

fused to IL15
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSNWVNVISDLKKIEDLIQSMHIDATLYTE

SDVHPSCKVTAMKCFLLELQVISLESGDASIHDTVENLIILANNSLSSNGNV

TESGCKECEELEEKNIKEFLQSFVHIVQMFINTS

SEQ ID NO: 725
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTS

anti-VEGF LC
SLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKV

fused to LIGHT
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSDGPAGSWEQLIQERRSHEVNPAAHLTG

ANSSLTGSGGPLLWETQLGLAFLRGLSYHDGALVVTKAGYYYIYSKVQLG

GVGCPLGLASTITHGLYKRTPRYPEELELLVSQQSPCGRATSSSRVWWDSS

FLGGVVHLEAGEKVVVRVLDERLVRLRDGTRSYFGAFMV

SEQ ID NO: 726
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTS

anti-VEGF LC
SLHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKV

fused to OX40L
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ

ECD
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT

KSFNRGECGGGGSGGGGSGGGGSQVSHRYPRIQSIKVQFTEYKKEKGFILT

SQKEDEIMKVQNNSVIINCDGFYLISLKGYFSQEVNISLHYQKDEEPLFQLK

KVRSVNSLMVASLTYKDKVYLNVTTDNTSLDDFHVNGGELILIHQNPGEFC

VL

SEQ ID NO: 727
DIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPPKLLI

CD3/CD19
YDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFG

BiTE-Fc-
GGTKLEIKGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGY

BTLAecd
AFSSYWMNWVKQRPGQGLEWIGQIWPGDGDTNYNGKFKGKATLTADESS

STAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYWGQGTTVTVSSG

GGGSDIKLQQSGAELARPGASVKMSCKTSGYTFTRYTMHWVKQRPGQGL

EWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYC

ARYYDDHYCLDYWGQGTTLTVSSVEGGSGGSGGSGGSGGVDDIQLTQSPA

IMSASPGEKVTMTCRASSSVSYMNWYQQKSGTSPKRWIYDTSKVASGVPY

RFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELKASTK

GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSKESCDVQLYIKRQS

EHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNI

SFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEM

AS

SEQ ID NO: 728
DIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPPKLLI

CD3/CD19
YDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFG

BiTE-BTLAecd
GGTKLEIKGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGY

AFSSYWMNWVKQRPGQGLEWIGQIWPGDGDTNYNGKFKGKATLTADESS

STAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYWGQGTTVTVSSG

GGGSDIKLQQSGAELARPGASVKMSCKTSGYTFTRYTMHWVKQRPGQGL

EWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYC

ARYYDDHYCLDYWGQGTTLTVSSVEGGSGGSGGSGGSGGVDDIQLTQSPA

IMSASPGEKVTMTCRASSSVSYMNWYQQKSGTSPKRWIYDTSKVASGVPY

RFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELKGGGG

SGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVT

WCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQS

NLIESHSTTLYVTDVKSASERPSKDEMASHHHHHH

SEQ ID NO: 729
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVA

CD3/PSMA
IISDGGYYTYYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFP

BiTE-Fc-
LLRHGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASV

BTLAecd
GDRVTITCKASQNVDTNVAWYQQKPGQAPKSLIYSASYRYSDVPSRFSGSA

SGTDFTLTISSVQSEDFATYYCQQYDSYPYTFGGGTKLEIKSGGGGSEVQLV

ESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSK

YNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGN

FGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARF

SGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLASTK

GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSKESCDVQLYIKRQS

EHSILAGDPFELECPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNI

SFFILHFEPVLPNDNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEM

AS

SEQ ID NO: 730
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVA

CD3/PSMA
IISDGGYYTYYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFP

BiTE-BTLAecd
LLRHGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASV

GDRVTITCKASQNVDTNVAWYQQKPGQAPKSLIYSASYRYSDVPSRFSGSA

SGTDFTLTISSVQSEDFATYYCQQYDSYPYTFGGGTKLEIKSGGGGSEVQLV

ESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSK

YNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGN

FGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARF

SGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGG

SGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVT

WCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLPNDNGSYRCSANFQS

NLIESHSTTLYVTDVKSASERPSKDEMASHHHHHH

SEQ ID NO: 731
DIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPPKLLI

CD3/CD19
YDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFG

BiTE-Fc-PD1ecd
GGTKLEIKGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGY

AFSSYWMNWVKQRPGQGLEWIGQIWPGDGDTNYNGKFKGKATLTADESS

STAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYWGQGTTVTVSSG

GGGSDIKLQQSGAELARPGASVKMSCKTSGYTFTRYTMHWVKQRPGQGL

EWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYC

ARYYDDHYCLDYWGQGTTLTVSSVEGGSGGSGGSGGSGGVDDIQLTQSPA

IMSASPGEKVTMTCRASSSVSYMNWYQQKSGTSPKRWIYDTSKVASGVPY

RFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELKASTK

GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSPGWFLDSPDRPWN

PPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPED

RSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKE

SLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 732
DIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPPKLLI

CD3/CD19
YDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFG

BiTE-PD1ecd
GGTKLEIKGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGY

AFSSYWMNWVKQRPGQGLEWIGQIWPGDGDTNYNGKFKGKATLTADESS

STAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYWGQGTTVTVSSG

GGGSDIKLQQSGAELARPGASVKMSCKTSGYTFTRYTMHWVKQRPGQGL

EWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYC

ARYYDDHYCLDYWGQGTTLTVSSVEGGSGGSGGSGGSGGVDDIQLTQSPA

IMSASPGEKVTMTCRASSSVSYMNWYQQKSGTSPKRWIYDTSKVASGVPY

RFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELKGGGG

SGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTS

ESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSV

VRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRP

AGQFQTLVHHHHHH

SEQ ID NO: 733
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVA

CD3/PSMA
IISDGGYYTYYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFP

BiTE-Fc-PD1ecd
LLRHGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASV

GDRVTITCKASQNVDTNVAWYQQKPGQAPKSLIYSASYRYSDVPSRFSGSA

SGTDFTLTISSVQSEDFATYYCQQYDSYPYTFGGGTKLEIKSGGGGSEVQLV

ESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSK

YNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGN

FGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARF

SGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLASTK

GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSPGWFLDSPDRPWN

PPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPED

RSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKE

SLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 734
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVA

CD3/PSMA
IISDGGYYTYYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFP

BiTE-PD1ecd
LLRHGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASV

GDRVTITCKASQNVDTNVAWYQQKPGQAPKSLIYSASYRYSDVPSRFSGSA

SGTDFTLTISSVQSEDFATYYCQQYDSYPYTFGGGTKLEIKSGGGGSEVQLV

ESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSK

YNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGN

FGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARF

SGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGG

SGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTS

ESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSV

VRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRP

AGQFQTLVHHHHHH

SEQ ID NO: 735
DIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPPKLLI

CD3/CD19
YDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFG

BiTE-Fc-
GGTKLEIKGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGY

SIGLEC10ecd
AFSSYWMNWVKQRPGQGLEWIGQIWPGDGDTNYNGKFKGKATLTADESS

STAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYWGQGTTVTVSSG

GGGSDIKLQQSGAELARPGASVKMSCKTSGYTFTRYTMHWVKQRPGQGL

EWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYC

ARYYDDHYCLDYWGQGTTLTVSSVEGGSGGSGGSGGSGGVDDIQLTQSPA

IMSASPGEKVTMTCRASSSVSYMNWYQQKSGTSPKRWIYDTSKVASGVPY

RFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELKASTK

GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSMDGRFWIRVQESV

MVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQS

REVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYN

FMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWT

GAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRL

RVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPP

ATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQ

RALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTH

SSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQ

HVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEG

NSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQ

LPDKKGLIST

SEQ ID NO: 736
DIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPPKLLI

CD3/CD19
YDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFG

BiTE-
GGTKLEIKGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGY

SIGLEC10ecd
AFSSYWMNWVKQRPGQGLEWIGQIWPGDGDTNYNGKFKGKATLTADESS

STAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYWGQGTTVTVSSG

GGGSDIKLQQSGAELARPGASVKMSCKTSGYTFTRYTMHWVKQRPGQGL

EWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYC

ARYYDDHYCLDYWGQGTTLTVSSVEGGSGGSGGSGGSGGVDDIQLTQSPA

IMSASPGEKVTMTCRASSSVSYMNWYQQKSGTSPKRWIYDTSKVASGVPY

RFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELKGGGG

SGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTP

AYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVI

RDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLE

PGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQ

DHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQ

GNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGL

ELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTV

LENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGV

LELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGL

HCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHG

GLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLISTHHHHHH

SEQ ID NO: 737
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVA

CD3/PSMA
IISDGGYYTYYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFP

BiTE-Fc-
LLRHGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASV

SIGLEC10ecd
GDRVTITCKASQNVDTNVAWYQQKPGQAPKSLIYSASYRYSDVPSRFSGSA

SGTDFTLTISSVQSEDFATYYCQQYDSYPYTFGGGTKLEIKSGGGGSEVQLV

ESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSK

YNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGN

FGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARF

SGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLASTK

GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSMDGRFWIRVQESV

MVPEGLCISVPCSFSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQS

REVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYN

FMNDGFFLKVTALTQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWT

GAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRL

RVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPP

ATLSWVLQNRVLSSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQ

RALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTH

SSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQ

HVSLSLSVHYSPKLLGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEG

NSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQ

LPDKKGLIST

SEQ ID NO: 738
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVA

CD3/PSMA
IISDGGYYTYYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFP

BiTE-
LLRHGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASV

SIGLEC10ecd
GDRVTITCKASQNVDTNVAWYQQKPGQAPKSLIYSASYRYSDVPSRFSGSA

SGTDFTLTISSVQSEDFATYYCQQYDSYPYTFGGGTKLEIKSGGGGSEVQLV

ESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSK

YNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGN

FGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARF

SGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGG

SGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTP

AYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVI

RDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLE

PGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQ

DHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQ

GNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGL

ELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTV

LENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGV

LELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGL

HCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHG

GLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLISTHHHHHH

SEQ ID NO: 739
DIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPPKLLI

CD3/CD19
YDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFG

BiTE-Fc-
GGTKLEIKGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGY

SIRPaecd
AFSSYWMNWVKQRPGQGLEWIGQIWPGDGDTNYNGKFKGKATLTADESS

STAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYWGQGTTVTVSSG

GGGSDIKLQQSGAELARPGASVKMSCKTSGYTFTRYTMHWVKQRPGQGL

EWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYC

ARYYDDHYCLDYWGQGTTLTVSSVEGGSGGSGGSGGSGGVDDIQLTQSPA

IMSASPGEKVTMTCRASSSVSYMNWYQQKSGTSPKRWIYDTSKVASGVPY

RFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELKASTK

GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSEEELQVIQPDKSVL

VAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDL

TKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAK

PS

SEQ ID NO: 740
DIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPPKLLI

CD3/CD19
YDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFG

BiTE-SIRPaecd
GGTKLEIKGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGY

AFSSYWMNWVKQRPGQGLEWIGQIWPGDGDTNYNGKFKGKATLTADESS

STAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYWGQGTTVTVSSG

GGGSDIKLQQSGAELARPGASVKMSCKTSGYTFTRYTMHWVKQRPGQGL

EWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYC

ARYYDDHYCLDYWGQGTTLTVSSVEGGSGGSGGSGGSGGVDDIQLTQSPA

IMSASPGEKVTMTCRASSSVSYMNWYQQKSGTSPKRWIYDTSKVASGVPY

RFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELKGGGG

SGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRG

AGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCV

KFRKGSPDDVEFKSGAGTELSVRAKPSHHHHHH

SEQ ID NO: 741
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVA

CD3/PSMA
IISDGGYYTYYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFP

BiTE-Fc-
LLRHGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASV

SIRPaecd
GDRVTITCKASQNVDTNVAWYQQKPGQAPKSLIYSASYRYSDVPSRFSGSA

SGTDFTLTISSVQSEDFATYYCQQYDSYPYTFGGGTKLEIKSGGGGSEVQLV

ESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSK

YNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGN

FGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARF

SGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLASTK

GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSEEELQVIQPDKSVL

VAAGETATLRCTATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDL

TKRNNMDFSIRIGNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAK

PS

SEQ ID NO: 742
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVA

CD3/PSMA
IISDGGYYTYYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFP

BiTE-SIRPaecd
LLRHGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASV

GDRVTITCKASQNVDTNVAWYQQKPGQAPKSLIYSASYRYSDVPSRFSGSA

SGTDFTLTISSVQSEDFATYYCQQYDSYPYTFGGGTKLEIKSGGGGSEVQLV

ESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSK

YNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGN

FGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARF

SGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGG

SGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRG

AGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCV

KFRKGSPDDVEFKSGAGTELSVRAKPSHHHHHH

SEQ ID NO: 743
DIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPPKLLI

CD3/CD19
YDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFG

BiTE-Fc-
GGTKLEIKGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGY

TIM3ecd
AFSSYWMNWVKQRPGQGLEWIGQIWPGDGDTNYNGKFKGKATLTADESS

STAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYWGQGTTVTVSSG

GGGSDIKLQQSGAELARPGASVKMSCKTSGYTFTRYTMHWVKQRPGQGL

EWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYC

ARYYDDHYCLDYWGQGTTLTVSSVEGGSGGSGGSGGSGGVDDIQLTQSPA

IMSASPGEKVTMTCRASSSVSYMNWYQQKSGTSPKRWIYDTSKVASGVPY

RFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELKASTK

GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSSEVEYRAEVGQNA

YLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYW

LNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTP

APTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRL

ANDLRDSGATIRIG

SEQ ID NO: 744
DIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPPKLLI

CD3/CD19
YDASNLVSGIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFG

BiTE-TIM3ecd
GGTKLEIKGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGY

AFSSYWMNWVKQRPGQGLEWIGQIWPGDGDTNYNGKFKGKATLTADESS

STAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYWGQGTTVTVSSG

GGGSDIKLQQSGAELARPGASVKMSCKTSGYTFTRYTMHWVKQRPGQGL

EWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYC

ARYYDDHYCLDYWGQGTTLTVSSVEGGSGGSGGSGGSGGVDDIQLTQSPA

IMSASPGEKVTMTCRASSSVSYMNWYQQKSGTSPKRWIYDTSKVASGVPY

RFSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELKGGGG

SGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACP

VFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYC

CRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAE

TQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIGHHHHHH

SEQ ID NO: 745
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVA

CD3/PSMA
IISDGGYYTYYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFP

BiTE-Fc-
LLRHGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASV

TIM3ecd
GDRVTITCKASQNVDTNVAWYQQKPGQAPKSLIYSASYRYSDVPSRFSGSA

SGTDFTLTISSVQSEDFATYYCQQYDSYPYTFGGGTKLEIKSGGGGSEVQLV

ESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSK

YNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGN

FGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARF

SGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLASTK

GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA

VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS

DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSSEVEYRAEVGQNA

YLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYW

LNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTP

APTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRL

ANDLRDSGATIRIG

SEQ ID NO: 746
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVA

CD3/PSMA
IISDGGYYTYYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFP

BiTE-TIM3ecd
LLRHGAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASV

GDRVTITCKASQNvDTNVAWYQQKPGQAPKSLIYSASYRYSDVPSRFSGSA

SGTDFTLTISSVQSEDFATYYCQQYDSYPYTFGGGTKLEIKSGGGGSEVQLV

ESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSK

YNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGN

FGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARF

SGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGG

SGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACP

VFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYC

CRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAE

TQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIGHHHHHH

SEQ ID NO: 747
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

a-
GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR

CEACAM5/CD3
WDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

HC1-BTLAecd
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREP

QVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANR

PHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHEEPVLPNDNGSYRCSA

NFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 748
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

a-
GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR

CEACAM5/CD3
WDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

HC2-BTLAecd
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDGGGGSGGGGSEVQLLESGGGLVQPG

GSLRLSCAASGFTFSTYAMNWVRQAPGKGLEWVSRIRSKYNNYATYYADS

VKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCVRHGNFGNSYVSWFAY

WGQGTLVTVSSASVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ

WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT

HQGLSSPVTKSFNRGECDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPC

RDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSKESCDVQLYIKRQSEHSILAGDPFELECPVKYCANRPHVTWCK

LNGTTCVKLEDRQTSWKEEKNISFFILHEEPVLPNDNGSYRCSANFQSNLIE

SHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 749
DIQMTQSPSSLSASVGDRVTITCKASAAVGTYVAWYQQKPGKAPKLLIYSA

a-
SYRKRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQYYTYPLFTFGQGT

CEACAM5/CD3
KLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA

LC1-BTLAecd
LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP

VTKSFNRGECGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFEL

ECPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLP

NDNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 750
QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTTSNYANWVQEKPGQAFRGLIG

a-
GTNKRAPGTPARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNLWVFG

CEACAM5/CD3
GGTKLTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW

LC2-BTLAecd
NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK

VDKKVEPKSCGGGGSGGGGSGGGGSKESCDVQLYIKRQSEHSILAGDPFEL

ECPVKYCANRPHVTWCKLNGTTCVKLEDRQTSWKEEKNISFFILHFEPVLP

NDNGSYRCSANFQSNLIESHSTTLYVTDVKSASERPSKDEMAS

SEQ ID NO: 751
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

a-
GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR

CEACAM5/CD3
WDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

HC1-PD1ecd
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREP

QVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSF

SNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDF

HMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPS

PSPRPAGQFQTLV

SEQ ID NO: 752
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

a-
GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR

CEACAM5/CD3
WDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

HC2-PD1ecd
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDGGGGSGGGGSEVQLLESGGGLVQPG

GSLRLSCAASGFTFSTYAMNWVRQAPGKGLEWVSRIRSKYNNYATYYADS

VKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCVRHGNFGNSYVSWFAY

WGQGTLVTVSSASVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ

WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT

HQGLSSPVTKSFNRGECDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPC

RDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFV

LNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRA

RRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQ

FQTLV

SEQ ID NO: 753
DIQMTQSPSSLSASVGDRVTITCKASAAVGTYVAWYQQKPGKAPKLLIYSA

a-
SYRKRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQYYTYPLFTFGQGT

CEACAM5/CD3
KLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA

LC1-PD1ecd
LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP

VTKSFNRGECGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVT

EGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFR

VTQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTER

RAEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 754
QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTTSNYANWVQEKPGQAFRGLIG

a-
GTNKRAPGTPARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNLWVFG

CEACAM5/CD3
GGTKLTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW

LC2-PD1ecd
NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK

VDKKVEPKSCGGGGSGGGGSGGGGSPGWFLDSPDRPWNPPTFSPALLVVT

EGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFR

VTQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTER

RAEVPTAHPSPSPRPAGQFQTLV

SEQ ID NO: 755
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

a-
GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR

CEACAM5/CD3
WDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

HC1-
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

SIGLEC10ecd
TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREP

QVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWT

GSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGN

CSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYI

PETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFT

PRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALE

PQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPR

PLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQA

NRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPS

DPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWE

AEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSL

SLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 756
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

a-
GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR

CEACAM5/CD3
WDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

HC2-
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

SIGLEC10ecd
TYICNVNHKPSNTKVDKKVEPKSCDGGGGSGGGGSEVQLLESGGGLVQPG

GSLRLSCAASGFTFSTYAMNWVRQAPGKGLEWVSRIRSKYNNYATYYADS

VKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCVRHGNFGNSYVSWFAY

WGQGTLVTVSSASVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ

WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT

HQGLSSPVTKSFNRGECDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPC

RDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSMDGRFWIRVQESVMVPEGLCISVPCSFSYPRQDWTGSTPAYG

YWFKAVTETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDA

QMQDESQYFFRVERGSYVRYNFMNDGFFLKVTALTQKPDVYIPETLEPGQ

PVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHN

TDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNV

PYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVLSSSHPWGPRPLGLELPG

VKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQANRTVLEN

LGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRGQVLSPSQPSDPGVLELP

RVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPSCSWEAEGLHCSC

SSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSS

GLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 757
DIQMTQSPSSLSASVGDRVTITCKASAAVGTYVAWYQQKPGKAPKLLIYSA

a-
SYRKRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQYYTYPLFTFGQGT

CEACAM5/CD3
KLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA

LC1-
LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP

SIGLEC10ecd
VTKSFNRGECGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPC

SFSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQ

LTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTA

LTQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPT

TSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISI

SRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVL

SSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 758
QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTTSNYANWVQEKPGQAFRGLIG

a-
GTNKRAPGTPARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNLWVFG

CEACAM5/CD3
GGTKLTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW

LC2-
NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK

SIGLEC10ecd
VDKKVEPKSCGGGGSGGGGSGGGGSMDGRFWIRVQESVMVPEGLCISVPC

SFSYPRQDWTGSTPAYGYWFKAVTETTKGAPVATNHQSREVEMSTRGRFQ

LTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYNFMNDGFFLKVTA

LTQKPDVYIPETLEPGQPVTVICVFNWAFEECPPPSFSWTGAALSSQGTKPT

TSHFSVLSFTPRPQDHNTDLTCHVDFSRKGVSAQRTVRLRVAYAPRDLVISI

SRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVL

SSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPEN

LRVMVSQANRTVLENLGNGTSLPVLEGQSLCLVCVTHSSPPARLSWTQRG

QVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKL

LGPSCSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSA

GPWANSSLSLHGGLSSGLRLRCEAWNVHGAQSGSILQLPDKKGLIST

SEQ ID NO: 759
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

a-
GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR

CEACAM5/CD3
WDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

HC1-SIRPaecd
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREP

QVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQ

WFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGT

YYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 760
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

a-
GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR

CEACAM5/CD3
WDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

HC2-SIRPaecd
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDGGGGSGGGGSEVQLLESGGGLVQPG

GSLRLSCAASGFTFSTYAMNWVRQAPGKGLEWVSRIRSKYNNYATYYADS

VKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCVRHGNFGNSYVSWFAY

WGQGTLVTVSSASVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ

WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT

HQGLSSPVTKSFNRGECDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPC

RDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSEEELQVIQPDKSVLVAAGETATLRCTATSLIPVGPIQWFRGAGP

GRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYYCVKFR

KGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 761
DIQMTQSPSSLSASVGDRVTITCKASAAVGTYVAWYQQKPGKAPKLLIYSA

a-
SYRKRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQYYTYPLFTFGQGT

CEACAM5/CD3
KLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA

LC1-SIRPaecd
LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP

VTKSFNRGECGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRC

TATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIR

IGNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 762
QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTTSNYANWVQEKPGQAFRGLIG

a-
GTNKRAPGTPARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNLWVFG

CEACAM5/CD3
GGTKLTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW

LC2-SIRPaecd
NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK

VDKKVEPKSCGGGGSGGGGSGGGGSEEELQVIQPDKSVLVAAGETATLRC

TATSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIR

IGNITPADAGTYYCVKFRKGSPDDVEFKSGAGTELSVRAKPS

SEQ ID NO: 763
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

a-
GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR

CEACAM5/CD3
WDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

HC1-TGFbRecd
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREP

QVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVR

FSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPY

HDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 764
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

a-
GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR

CEACAM5/CD3
WDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

HC2-TGFbRecd
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDGGGGSGGGGSEVQLLESGGGLVQPG

GSLRLSCAASGFTFSTYAMNWVRQAPGKGLEWVSRIRSKYNNYATYYADS

VKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCVRHGNFGNSYVSWFAY

WGQGTLVTVSSASVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ

WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT

HQGLSSPVTKSFNRGECDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPC

RDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSTIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQ

KSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDA

ASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD

SEQ ID NO: 765
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

a-
GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR

CEACAM5/CD3
WDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

HC1-TIM3ecd
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREP

QVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGK

GACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADS

GIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGH

GPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 766
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

a-
GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR

CEACAM5/CD3
WDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

HC2-TIM3ecd
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDGGGGSGGGGSEVQLLESGGGLVQPG

GSLRLSCAASGFTFSTYAMNWVRQAPGKGLEWVSRIRSKYNNYATYYADS

VKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCVRHGNFGNSYVSWFAY

WGQGTLVTVSSASVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ

WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT

HQGLSSPVTKSFNRGECDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPC

RDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFEC

GNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQI

PGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTL

GSLPDINLTQISTLANELRDSRLANDLRDSGATIRIG

SEQ ID NO: 767
DIQMTQSPSSLSASVGDRVTITCKASAAVGTYVAWYQQKPGKAPKLLIYSA

a-
SYRKRGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQYYTYPLFTFGQGT

CEACAM5/CD3
KLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA

LC1-TIM3ecd
LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSP

VTKSFNRGECGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPG

NLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVS

LTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAA

FPRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATI

RIG

SEQ ID NO: 768
QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTTSNYANWVQEKPGQAFRGLIG

a-
GTNKRAPGTPARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNLWVFG

CEACAM5/CD3
GGTKLTVLSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW

LC2-TIM3ecd
NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK

VDKKVEPKSCGGGGSGGGGSGGGGSSEVEYRAEVGQNAYLPCFYTPAAPG

NLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVS

LTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAA

FPRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATI

RIG

SEQ ID NO: 769
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

a-
GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR

CEACAM5/CD3
WDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

HC1-VEGFRecd
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREP

QVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGGGSGGGGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNIT

VTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTN

YLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSS

KHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMT

KKNSTFVRVHEK

SEQ ID NO: 770
QVQLVQSGAEVKKPGASVKVSCKASGYTFTEFGMNWVRQAPGQGLEWM

a-
GWINTKTGEATYVEEFKGRVTFTTDTSTSTAYMELRSLRSDDTAVYYCAR

CEACAM5/CD3
WDFAYYVEAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

HC2-VEGFRecd
LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ

TYICNVNHKPSNTKVDKKVEPKSCDGGGGSGGGGSEVQLLESGGGLVQPG

GSLRLSCAASGFTFSTYAMNWVRQAPGKGLEWVSRIRSKYNNYATYYADS

VKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCVRHGNFGNSYVSWFAY

WGQGTLVTVSSASVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ

WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT

HQGLSSPVTKSFNRGECDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPC

RDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFP

LDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQT

NTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKL

VNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVR

VHEK

Sequences of the Alts of the present invention are found in Table 2.

TABLE 2

Fusion protein of the invention
Sequence IDs

anti-EGFR-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 220

(cetuximab)
light chain = SEQ ID NO: 221

anti-EGFR-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 220

(cetuximab)
light chain = SEQ ID NO: 222

anti-EGFR-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 220

(cetuximab)
light chain = SEQ ID NO: 223

anti-EGFR-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 220

(cetuximab)
light chain = SEQ ID NO: 224

anti-EGFR-BTLAecd
heavy chain = SEQ ID NO: 220

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFR-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 225

(cetuximab)
light chain = SEQ ID NO: 226

anti-EGFR-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 225

(cetuximab)
light chain = SEQ ID NO: 222

anti-EGFR-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 225

(cetuximab)
light chain = SEQ ID NO: 223

anti-EGFR-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 225

(cetuximab)
light chain = SEQ ID NO: 224

anti-EGFR-PD1ecd
heavy chain = SEQ ID NO: 225

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFR-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 227

(cetuximab)
light chain = SEQ ID NO: 226

anti-EGFR-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 227

(cetuximab)
light chain = SEQ ID NO: 221

anti-EGFR-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 227

(cetuximab)
light chain = SEQ ID NO: 223

anti-EGFR-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 227

(cetuximab)
light chain = SEQ ID NO: 224

anti-EGFR-SIGLEC10ecd
heavy chain = SEQ ID NO: 227

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFR-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 228

(cetuximab)
light chain = SEQ ID NO: 226

anti-EGFR-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 228

(cetuximab)
light chain = SEQ ID NO: 221

anti-EGFR-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 228

(cetuximab)
light chain = SEQ ID NO: 222

anti-EGFR-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 228

(cetuximab)
light chain = SEQ ID NO: 224

anti-EGFR-SIRPaecd
heavy chain = SEQ ID NO: 228

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFR-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 229

(cetuximab)
light chain = SEQ ID NO: 226

anti-EGFR-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 229

(cetuximab)
light chain = SEQ ID NO: 221

anti-EGFR-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 229

(cetuximab)
light chain = SEQ ID NO: 222

anti-EGFR-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 229

(cetuximab)
light chain = SEQ ID NO: 223

anti-EGFR-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 229

(cetuximab)
light chain = SEQ ID NO: 224

anti-EGFR-TGFbRecd
heavy chain = SEQ ID NO: 229

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFR-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 230

(cetuximab)
light chain = SEQ ID NO: 226

anti-EGFR-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 230

(cetuximab)
light chain = SEQ ID NO: 221

anti-EGFR-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 230

(cetuximab)
light chain = SEQ ID NO: 222

anti-EGFR-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 230

(cetuximab)
light chain = SEQ ID NO: 223

anti-EGFR-TIM3ecd
heavy chain = SEQ ID NO: 230

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFR-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 231

(cetuximab)
light chain = SEQ ID NO: 226

anti-EGFR-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 231

(cetuximab)
light chain = SEQ ID NO: 221

anti-EGFR-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 231

(cetuximab)
light chain = SEQ ID NO: 222

anti-EGFR-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 231

(cetuximab)
light chain = SEQ ID NO: 223

anti-EGFR-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 231

(cetuximab)
light chain = SEQ ID NO: 224

anti-EGFR-VEGFRecd
heavy chain = SEQ ID NO: 231

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFRvIII-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 232

(depatuxizumab)
light chain = SEQ ID NO: 233

anti-EGFRvIII-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 232

(depatuxizumab)
light chain = SEQ ID NO: 234

anti-EGFRvIII-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 232

(depatuxizumab)
light chain = SEQ ID NO: 235

anti-EGFRvIII-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 232

(depatuxizumab)
light chain = SEQ ID NO: 236

anti-EGFRvIII-BTLAecd
heavy chain = SEQ ID NO: 232

(depatuxizumab)
light chain = SEQ ID NO: 47

anti-EGFRvIII-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 237

(depatuxizumab)
light chain = SEQ ID NO: 238

anti-EGFRvIII-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 237

(depatuxizumab)
light chain = SEQ ID NO: 234

anti-EGFRvIII-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 237

(depatuxizumab)
light chain = SEQ ID NO: 235

anti-EGFRvIII-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 237

(depatuxizumab)
light chain = SEQ ID NO: 236

anti-EGFRvIII-PD1ecd
heavy chain = SEQ ID NO: 237

(depatuxizumab)
light chain = SEQ ID NO: 47

anti-EGFRvIII-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 239

(depatuxizumab)
light chain = SEQ ID NO: 238

anti-EGFRvIII-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 239

(depatuxizumab)
light chain = SEQ ID NO: 233

anti-EGFRvIII-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 239

(depatuxizumab)
light chain = SEQ ID NO: 235

anti-EGFRvIII-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 239

(depatuxizumab)
light chain = SEQ ID NO: 236

anti-EGFRvIII-SIGLEC10ecd
heavy chain = SEQ ID NO: 239

(depatuxizumab)
light chain = SEQ ID NO: 47

anti-EGFRvIII-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 240

(depatuxizumab)
light chain = SEQ ID NO: 238

anti-EGFRvIII-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 240

(depatuxizumab)
light chain = SEQ ID NO: 233

anti-EGFRvIII-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 240

(depatuxizumab)
light chain = SEQ ID NO: 234

anti-EGFRvIII-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 240

(depatuxizumab)
light chain = SEQ ID NO: 236

anti-EGFRvIII-SIRPaecd
heavy chain = SEQ ID NO: 240

(depatuxizumab)
light chain = SEQ ID NO: 47

anti-EGFRvIII-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 241

(depatuxizumab)
light chain = SEQ ID NO: 238

anti-EGFRvIII-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 241

(depatuxizumab)
light chain = SEQ ID NO: 233

anti-EGFRvIII-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 241

(depatuxizumab)
light chain = SEQ ID NO: 234

anti-EGFRvIII-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 241

(depatuxizumab)
light chain = SEQ ID NO: 235

anti-EGFRvIII-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 241

(depatuxizumab)
light chain = SEQ ID NO: 236

anti-EGFRvIII-TGFbRecd
heavy chain = SEQ ID NO: 241

(depatuxizumab)
light chain = SEQ ID NO: 47

anti-EGFRvIII-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 242

(depatuxizumab)
light chain = SEQ ID NO: 238

anti-EGFRvIII-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 242

(depatuxizumab)
light chain = SEQ ID NO: 233

anti-EGFRvIII-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 242

(depatuxizumab)
light chain = SEQ ID NO: 234

anti-EGFRvIII-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 242

(depatuxizumab)
light chain = SEQ ID NO: 235

anti-EGFRvIII-TIM3ecd
heavy chain = SEQ ID NO: 242

(depatuxizumab)
light chain = SEQ ID NO: 47

anti-EGFRvIII-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 243

(depatuxizumab)
light chain = SEQ ID NO: 238

anti-EGFRvIII-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 243

(depatuxizumab)
light chain = SEQ ID NO: 233

anti-EGFRvIII-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 243

(depatuxizumab)
light chain = SEQ ID NO: 234

anti-EGFRvIII-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 243

(depatuxizumab)
light chain = SEQ ID NO: 235

anti-EGFRvIII-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 243

(depatuxizumab)
light chain = SEQ ID NO: 236

anti-EGFRvIII-VEGFRecd
heavy chain = SEQ ID NO: 243

(depatuxizumab)
light chain = SEQ ID NO: 47

anti-HER2-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 244

(trastuzumab)
light chain = SEQ ID NO: 245

anti-HER2-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 244

(trastuzumab)
light chain = SEQ ID NO: 246

anti-HER2-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 244

(trastuzumab)
light chain = SEQ ID NO: 247

anti-HER2-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 244

(trastuzumab)
light chain = SEQ ID NO: 248

anti-HER2-BTLAecd
heavy chain = SEQ ID NO: 244

(trastuzumab)
light chain = SEQ ID NO: 55

anti-HER2-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 249

(trastuzumab)
light chain = SEQ ID NO: 250

anti-HER2-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 249

(trastuzumab)
light chain = SEQ ID NO: 246

anti-HER2-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 249

(trastuzumab)
light chain = SEQ ID NO: 247

anti-HER2-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 249

(trastuzumab)
light chain = SEQ ID NO: 248

anti-HER2-PD1ecd
heavy chain = SEQ ID NO: 249

(trastuzumab)
light chain = SEQ ID NO: 55

anti-HER2-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 251

(trastuzumab)
light chain = SEQ ID NO: 250

anti-HER2-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 251

(trastuzumab)
light chain = SEQ ID NO: 245

anti-HER2-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 251

(trastuzumab)
light chain = SEQ ID NO: 247

anti-HER2-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 251

(trastuzumab)
light chain = SEQ ID NO: 248

anti-HER2-SIGLEC10ecd
heavy chain = SEQ ID NO: 251

(trastuzumab)
light chain = SEQ ID NO: 55

anti-HER2-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 252

(trastuzumab)
light chain = SEQ ID NO: 250

anti-HER2-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 252

(trastuzumab)
light chain = SEQ ID NO: 245

anti-HER2-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 252

(trastuzumab)
light chain = SEQ ID NO: 246

anti-HER2-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 252

(trastuzumab)
light chain = SEQ ID NO: 248

anti-HER2-SIRPaecd
heavy chain = SEQ ID NO: 252

(trastuzumab)
light chain = SEQ ID NO: 55

anti-HER2-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 253

(trastuzumab)
light chain = SEQ ID NO: 250

anti-HER2-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 253

(trastuzumab)
light chain = SEQ ID NO: 245

anti-HER2-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 253

(trastuzumab)
light chain = SEQ ID NO: 246

anti-HER2-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 253

(trastuzumab)
light chain = SEQ ID NO: 247

anti-HER2-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 253

(trastuzumab)
light chain = SEQ ID NO: 248

anti-HER2-TGFbRecd
heavy chain = SEQ ID NO: 253

(trastuzumab)
light chain = SEQ ID NO: 55

anti-HER2-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 254

(trastuzumab)
light chain = SEQ ID NO: 250

anti-HER2-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 254

(trastuzumab)
light chain = SEQ ID NO: 245

anti-HER2-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 254

(trastuzumab)
light chain = SEQ ID NO: 246

anti-HER2-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 254

(trastuzumab)
light chain = SEQ ID NO: 247

anti-HER2-TIM3ecd
heavy chain = SEQ ID NO: 254

(trastuzumab)
light chain = SEQ ID NO: 55

anti-HER2-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 255

(trastuzumab)
light chain = SEQ ID NO: 250

anti-HER2-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 255

(trastuzumab)
light chain = SEQ ID NO: 245

anti-HER2-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 255

(trastuzumab)
light chain = SEQ ID NO: 246

anti-HER2-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 255

(trastuzumab)
light chain = SEQ ID NO: 247

anti-HER2-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 255

(trastuzumab)
light chain = SEQ ID NO: 248

anti-HER2-VEGFRecd
heavy chain = SEQ ID NO: 255

(trastuzumab)
light chain = SEQ ID NO: 55

anti-nectin4-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 256

(enfortumab)
light chain = SEQ ID NO: 257

anti-nectin4-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 256

(enfortumab)
light chain = SEQ ID NO: 258

anti-nectin4-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 256

(enfortumab)
light chain = SEQ ID NO: 259

anti-nectin4-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 256

(enfortumab)
light chain = SEQ ID NO: 260

anti-nectin4-BTLAecd
heavy chain = SEQ ID NO: 256

(enfortumab)
light chain = SEQ ID NO: 160

anti-nectin4-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 261

(enfortumab)
light chain = SEQ ID NO: 262

anti-nectin4-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 261

(enfortumab)
light chain = SEQ ID NO: 258

anti-nectin4-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 261

(enfortumab)
light chain = SEQ ID NO: 259

anti-nectin4-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 261

(enfortumab)
light chain = SEQ ID NO: 260

anti-nectin4-PD1ecd
heavy chain = SEQ ID NO: 261

(enfortumab)
light chain = SEQ ID NO: 160

anti-nectin4-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 263

(enfortumab)
light chain = SEQ ID NO: 262

anti-nectin4-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 263

(enfortumab)
light chain = SEQ ID NO: 257

anti-nectin4-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 263

(enfortumab)
light chain = SEQ ID NO: 259

anti-nectin4-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 263

(enfortumab)
light chain = SEQ ID NO: 260

anti-nectin4-SIGLEC10ecd
heavy chain = SEQ ID NO: 263

(enfortumab)
light chain = SEQ ID NO: 160

anti-nectin4-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 264

(enfortumab)
light chain = SEQ ID NO: 262

anti-nectin4-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 264

(enfortumab)
light chain = SEQ ID NO: 257

anti-nectin4-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 264

(enfortumab)
light chain = SEQ ID NO: 258

anti-nectin4-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 264

(enfortumab)
light chain = SEQ ID NO: 260

anti-nectin4-SIRPaecd
heavy chain = SEQ ID NO: 264

(enfortumab)
light chain = SEQ ID NO: 160

anti-nectin4-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 265

(enfortumab)
light chain = SEQ ID NO: 262

anti-nectin4-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 265

(enfortumab)
light chain = SEQ ID NO: 257

anti-nectin4-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 265

(enfortumab)
light chain = SEQ ID NO: 258

anti-nectin4-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 265

(enfortumab)
light chain = SEQ ID NO: 259

anti-nectin4-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 265

(enfortumab)
light chain = SEQ ID NO: 260

anti-nectin4-TGFbRecd
heavy chain = SEQ ID NO: 265

(enfortumab)
light chain = SEQ ID NO: 160

anti-nectin4-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 266

(enfortumab)
light chain = SEQ ID NO: 262

anti-nectin4-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 266

(enfortumab)
light chain = SEQ ID NO: 257

anti-nectin4-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 266

(enfortumab)
light chain = SEQ ID NO: 258

anti-nectin4-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 266

(enfortumab)
light chain = SEQ ID NO: 259

anti-nectin4-TIM3ecd
heavy chain = SEQ ID NO: 266

(enfortumab)
light chain = SEQ ID NO: 160

anti-nectin4-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 267

(enfortumab)
light chain = SEQ ID NO: 262

anti-nectin4-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 267

(enfortumab)
light chain = SEQ ID NO: 257

anti-nectin4-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 267

(enfortumab)
light chain = SEQ ID NO: 258

anti-nectin4-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 267

(enfortumab)
light chain = SEQ ID NO: 259

anti-nectin4-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 267

(enfortumab)
light chain = SEQ ID NO: 260

anti-nectin4-VEGFRecd
heavy chain = SEQ ID NO: 267

(enfortumab)
light chain = SEQ ID NO: 160

anti-uPAR-BTLAecd
heavy chain = SEQ ID NO: 268

(ab1)
light chain = SEQ ID NO: 162

anti-uPAR-PD1ecd
heavy chain = SEQ ID NO: 269

(ab1)
light chain = SEQ ID NO: 162

anti-uPAR-SIGLEC10ecd
heavy chain = SEQ ID NO: 270

(ab1)
light chain = SEQ ID NO: 162

anti-uPAR-SIRPaecd
heavy chain = SEQ ID NO: 271

(ab1)
light chain = SEQ ID NO: 162

anti-uPAR-TGFbRecd
heavy chain = SEQ ID NO: 272

(ab1)
light chain = SEQ ID NO: 162

anti-uPAR-TIM3ecd
heavy chain = SEQ ID NO: 273

(ab1)
light chain = SEQ ID NO: 162

anti-uPAR-VEGFRecd
heavy chain = SEQ ID NO: 274

(ab1)
light chain = SEQ ID NO: 162

anti-PSMA-BTLAecd
heavy chain = SEQ ID NO: 275

(ab1)
light chain = SEQ ID NO: 121

anti-PSMA-PD1ecd
heavy chain = SEQ ID NO: 276

(ab1)
light chain = SEQ ID NO: 121

anti-PSMA-SIGLEC10ecd
heavy chain = SEQ ID NO: 277

(ab1)
light chain = SEQ ID NO: 121

anti-PSMA-SIRPaecd
heavy chain = SEQ ID NO: 278

(ab1)
light chain = SEQ ID NO: 121

anti-PSMA-TGFbRecd
heavy chain = SEQ ID NO: 279

(ab1)
light chain = SEQ ID NO: 121

anti-PSMA-TIM3ecd
heavy chain = SEQ ID NO: 280

(ab1)
light chain = SEQ ID NO: 121

anti-PSMA-VEGFRecd
heavy chain = SEQ ID NO: 281

(ab1)
light chain = SEQ ID NO: 121

anti-CEACAM5-BTLAecd
heavy chain = SEQ ID NO: 282

(labetuzumab)
light chain = SEQ ID NO: 26

anti-CEACAM5-PD1ecd
heavy chain = SEQ ID NO: 283

(labetuzumab)
light chain = SEQ ID NO: 26

anti-CEACAM5-SIGLEC10ecd
heavy chain = SEQ ID NO: 284

(labetuzumab)
light chain = SEQ ID NO: 26

anti-CEACAM5-SIRPaecd
heavy chain = SEQ ID NO: 285

(labetuzumab)
light chain = SEQ ID NO: 26

anti-CEACAM5-TGFbRecd
heavy chain = SEQ ID NO: 286

(labetuzumab)
light chain = SEQ ID NO: 26

anti-CEACAM5-TIM3ecd
heavy chain = SEQ ID NO: 287

(labetuzumab)
light chain = SEQ ID NO: 26

anti-CEACAM5-VEGFRecd
heavy chain = SEQ ID NO: 288

(labetuzumab)
light chain = SEQ ID NO: 26

anti-CD38-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 289

(daratumumab)
light chain = SEQ ID NO: 290

anti-CD38-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 289

(daratumumab)
light chain = SEQ ID NO: 291

anti-CD38-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 289

(daratumumab)
light chain = SEQ ID NO: 292

anti-CD38-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 289

(daratumumab)
light chain = SEQ ID NO: 293

anti-CD38-BTLAecd
heavy chain = SEQ ID NO: 289

(daratumumab)
light chain = SEQ ID NO: 16

anti-CD38-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 294

(daratumumab)
light chain = SEQ ID NO: 295

anti-CD38-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 294

(daratumumab)
light chain = SEQ ID NO: 291

anti-CD38-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 294

(daratumumab)
light chain = SEQ ID NO: 292

anti-CD38-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 294

(daratumumab)
light chain = SEQ ID NO: 293

anti-CD38-PD1ecd
heavy chain = SEQ ID NO: 294

(daratumumab)
light chain = SEQ ID NO: 16

anti-CD38-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 296

(daratumumab)
light chain = SEQ ID NO: 295

anti-CD38-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 296

(daratumumab)
light chain = SEQ ID NO: 290

anti-CD38-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 296

(daratumumab)
light chain = SEQ ID NO: 292

anti-CD38-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 296

(daratumumab)
light chain = SEQ ID NO: 293

anti-CD38-SIGLEC10ecd
heavy chain = SEQ ID NO: 296

(daratumumab)
light chain = SEQ ID NO: 16

anti-CD38-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 297

(daratumumab)
light chain = SEQ ID NO: 295

anti-CD38-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 297

(daratumumab)
light chain = SEQ ID NO: 290

anti-CD38-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 297

(daratumumab)
light chain = SEQ ID NO: 291

anti-CD38-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 297

(daratumumab)
light chain = SEQ ID NO: 293

anti-CD38-SIRPaecd
heavy chain = SEQ ID NO: 297

(daratumumab)
light chain = SEQ ID NO: 16

anti-CD38-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 298

(daratumumab)
light chain = SEQ ID NO: 295

anti-CD38-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 298

(daratumumab)
light chain = SEQ ID NO: 290

anti-CD38-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 298

(daratumumab)
light chain = SEQ ID NO: 291

anti-CD38-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 298

(daratumumab)
light chain = SEQ ID NO: 292

anti-CD38-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 298

(daratumumab)
light chain = SEQ ID NO: 293

anti-CD38-TGFbRecd
heavy chain = SEQ ID NO: 298

(daratumumab)
light chain = SEQ ID NO: 16

anti-CD38-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 299

(daratumumab)
light chain = SEQ ID NO: 295

anti-CD38-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 299

(daratumumab)
light chain = SEQ ID NO: 290

anti-CD38-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 299

(daratumumab)
light chain = SEQ ID NO: 291

anti-CD38-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 299

(daratumumab)
light chain = SEQ ID NO: 292

anti-CD38-TIM3ecd
heavy chain = SEQ ID NO: 299

(daratumumab)
light chain = SEQ ID NO: 16

anti-CD38-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 300

(daratumumab)
light chain = SEQ ID NO: 295

anti-CD38-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 300

(daratumumab)
light chain = SEQ ID NO: 290

anti-CD38-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 300

(daratumumab)
light chain = SEQ ID NO: 291

anti-CD38-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 300

(daratumumab)
light chain = SEQ ID NO: 292

anti-CD38-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 300

(daratumumab)
light chain = SEQ ID NO: 293

anti-CD38-VEGFRecd
heavy chain = SEQ ID NO: 300

(daratumumab)
light chain = SEQ ID NO: 16

anti-SLAMF7-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 301

(elotuzumab)
light chain = SEQ ID NO: 302

anti-SLAMF7-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 301

(elotuzumab)
light chain = SEQ ID NO: 303

anti-SLAMF7-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 301

(elotuzumab)
light chain = SEQ ID NO: 304

anti-SLAMF7-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 301

(elotuzumab)
light chain = SEQ ID NO: 305

anti-SLAMF7-BTLAecd
heavy chain = SEQ ID NO: 301

(elotuzumab)
light chain = SEQ ID NO: 127

anti-SLAMF7-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 306

(elotuzumab)
light chain = SEQ ID NO: 307

anti-SLAMF7-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 306

(elotuzumab)
light chain = SEQ ID NO: 303

anti-SLAMF7-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 306

(elotuzumab)
light chain = SEQ ID NO: 304

anti-SLAMF7-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 306

(elotuzumab)
light chain = SEQ ID NO: 305

anti-SLAMF7-PD1ecd
heavy chain = SEQ ID NO: 306

(elotuzumab)
light chain = SEQ ID NO: 127

anti-SLAMF7-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 308

(elotuzumab)
light chain = SEQ ID NO: 307

anti-SLAMF7-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 308

(elotuzumab)
light chain = SEQ ID NO: 302

anti-SLAMF7-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 308

(elotuzumab)
light chain = SEQ ID NO: 304

anti-SLAMF7-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 308

(elotuzumab)
light chain = SEQ ID NO: 305

anti-SLAMF7-SIGLEC10ecd
heavy chain = SEQ ID NO: 308

(elotuzumab)
light chain = SEQ ID NO: 127

anti-SLAMF7-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 309

(elotuzumab)
light chain = SEQ ID NO: 307

anti-SLAMF7-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 309

(elotuzumab)
light chain = SEQ ID NO: 302

anti-SLAMF7-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 309

(elotuzumab)
light chain = SEQ ID NO: 303

anti-SLAMF7-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 309

(elotuzumab)
light chain = SEQ ID NO: 305

anti-SLAMF7-SIRPaecd
heavy chain = SEQ ID NO: 309

(elotuzumab)
light chain = SEQ ID NO: 127

anti-SLAMF7-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 310

(elotuzumab)
light chain = SEQ ID NO: 307

anti-SLAMF7-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 310

(elotuzumab)
light chain = SEQ ID NO: 302

anti-SLAMF7-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 310

(elotuzumab)
light chain = SEQ ID NO: 303

anti-SLAMF7-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 310

(elotuzumab)
light chain = SEQ ID NO: 304

anti-SLAMF7-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 310

(elotuzumab)
light chain = SEQ ID NO: 305

anti-SLAMF7-TGFbRecd
heavy chain = SEQ ID NO: 310

(elotuzumab)
light chain = SEQ ID NO: 127

anti-SLAMF7-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 311

(elotuzumab)
light chain = SEQ ID NO: 307

anti-SLAMF7-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 311

(elotuzumab)
light chain = SEQ ID NO: 302

anti-SLAMF7-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 311

(elotuzumab)
light chain = SEQ ID NO: 303

anti-SLAMF7-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 311

(elotuzumab)
light chain = SEQ ID NO: 304

anti-SLAMF7-TIM3ecd
heavy chain = SEQ ID NO: 311

(elotuzumab)
light chain = SEQ ID NO: 127

anti-SLAMF7-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 312

(elotuzumab)
light chain = SEQ ID NO: 307

anti-SLAMF7-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 312

(elotuzumab)
light chain = SEQ ID NO: 302

anti-SLAMF7-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 312

(elotuzumab)
light chain = SEQ ID NO: 303

anti-SLAMF7-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 312

(elotuzumab)
light chain = SEQ ID NO: 304

anti-SLAMF7-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 312

(elotuzumab)
light chain = SEQ ID NO: 305

anti-SLAMF7-VEGFRecd
heavy chain = SEQ ID NO: 312

(elotuzumab)
light chain = SEQ ID NO: 127

anti-IL6R-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 313

(tocilizumab)
light chain = SEQ ID NO: 314

anti-IL6R-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 313

(tocilizumab)
light chain = SEQ ID NO: 315

anti-IL6R-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 313

(tocilizumab)
light chain = SEQ ID NO: 316

anti-IL6R-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 313

(tocilizumab)
light chain = SEQ ID NO: 317

anti-IL6R-BTLAecd
heavy chain = SEQ ID NO: 313

(tocilizumab)
light chain = SEQ ID NO: 79

anti-IL6R-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 318

(tocilizumab)
light chain = SEQ ID NO: 319

anti-IL6R-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 318

(tocilizumab)
light chain = SEQ ID NO: 315

anti-IL6R-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 318

(tocilizumab)
light chain = SEQ ID NO: 316

anti-IL6R-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 318

(tocilizumab)
light chain = SEQ ID NO: 317

anti-IL6R-PD1ecd
heavy chain = SEQ ID NO: 318

(tocilizumab)
light chain = SEQ ID NO: 79

anti-IL6R-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 320

(tocilizumab)
light chain = SEQ ID NO: 319

anti-IL6R-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 320

(tocilizumab)
light chain = SEQ ID NO: 314

anti-IL6R-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 320

(tocilizumab)
light chain = SEQ ID NO: 316

anti-IL6R-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 320

(tocilizumab)
light chain = SEQ ID NO: 317

anti-IL6R-SIGLEC10ecd
heavy chain = SEQ ID NO: 320

(tocilizumab)
light chain = SEQ ID NO: 79

anti-IL6R-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 321

(tocilizumab)
light chain = SEQ ID NO: 319

anti-IL6R-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 321

(tocilizumab)
light chain = SEQ ID NO: 314

anti-IL6R-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 321

(tocilizumab)
light chain = SEQ ID NO: 315

anti-IL6R-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 321

(tocilizumab)
light chain = SEQ ID NO: 317

anti-IL6R-SIRPaecd
heavy chain = SEQ ID NO: 321

(tocilizumab)
light chain = SEQ ID NO: 79

anti-IL6R-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 322

(tocilizumab)
light chain = SEQ ID NO: 319

anti-IL6R-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 322

(tocilizumab)
light chain = SEQ ID NO: 314

anti-IL6R-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 322

(tocilizumab)
light chain = SEQ ID NO: 315

anti-IL6R-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 322

(tocilizumab)
light chain = SEQ ID NO: 316

anti-IL6R-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 322

(tocilizumab)
light chain = SEQ ID NO: 317

anti-IL6R-TGFbRecd
heavy chain = SEQ ID NO: 322

(tocilizumab)
light chain = SEQ ID NO: 79

anti-IL6R-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 323

(tocilizumab)
light chain = SEQ ID NO: 319

anti-IL6R-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 323

(tocilizumab)
light chain = SEQ ID NO: 314

anti-IL6R-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 323

(tocilizumab)
light chain = SEQ ID NO: 315

anti-IL6R-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 323

(tocilizumab)
light chain = SEQ ID NO: 316

anti-IL6R-TIM3ecd
heavy chain = SEQ ID NO: 323

(tocilizumab)
light chain = SEQ ID NO: 79

anti-IL6R-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 324

(tocilizumab)
light chain = SEQ ID NO: 319

anti-IL6R-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 324

(tocilizumab)
light chain = SEQ ID NO: 314

anti-IL6R-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 324

(tocilizumab)
light chain = SEQ ID NO: 315

anti-IL6R-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 324

(tocilizumab)
light chain = SEQ ID NO: 316

anti-IL6R-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 324

(tocilizumab)
light chain = SEQ ID NO: 317

anti-IL6R-VEGFRecd
heavy chain = SEQ ID NO: 324

(tocilizumab)
light chain = SEQ ID NO: 79

anti-IL17R-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 325

(brodalumab)
light chain = SEQ ID NO: 326

anti-IL17R-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 325

(brodalumab)
light chain = SEQ ID NO: 327

anti-IL17R-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 325

(brodalumab)
light chain = SEQ ID NO: 328

anti-IL17R-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 325

(brodalumab)
light chain = SEQ ID NO: 329

anti-IL17R-BTLAecd
heavy chain = SEQ ID NO: 325

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL17R-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 330

(brodalumab)
light chain = SEQ ID NO: 331

anti-IL17R-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 330

(brodalumab)
light chain = SEQ ID NO: 327

anti-IL17R-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 330

(brodalumab)
light chain = SEQ ID NO: 328

anti-IL17R-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 330

(brodalumab)
light chain = SEQ ID NO: 329

anti-IL17R-PD1ecd
heavy chain = SEQ ID NO: 330

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL17R-SIGLEC10cd-BTLAecd
heavy chain = SEQ ID NO: 332

(brodalumab)
light chain = SEQ ID NO: 331

anti-IL17R-SIGLEC10cd-PD1ecd
heavy chain = SEQ ID NO: 332

(brodalumab)
light chain = SEQ ID NO: 326

anti-IL17R-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 332

(brodalumab)
light chain = SEQ ID NO: 328

anti-IL17R-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 332

(brodalumab)
light chain = SEQ ID NO: 329

anti-IL17R-SIGLEC10ecd
heavy chain = SEQ ID NO: 332

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL17R-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 333

(brodalumab)
light chain = SEQ ID NO: 331

anti-IL17R-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 333

(brodalumab)
light chain = SEQ ID NO: 326

anti-IL17R-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 333

(brodalumab)
light chain = SEQ ID NO: 327

anti-IL17R-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 333

(brodalumab)
light chain = SEQ ID NO: 329

anti-IL17R-SIRPaecd
heavy chain = SEQ ID NO: 333

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL17R-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 334

(brodalumab)
light chain = SEQ ID NO: 331

anti-IL17R-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 334

(brodalumab)
light chain = SEQ ID NO: 326

anti-IL17R-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 334

(brodalumab)
light chain = SEQ ID NO: 327

anti-IL17R-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 334

(brodalumab)
light chain = SEQ ID NO: 328

anti-IL17R-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 334

(brodalumab)
light chain = SEQ ID NO: 329

anti-IL17R-TGFbRecd
heavy chain = SEQ ID NO: 334

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL17R-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 335

(brodalumab)
light chain = SEQ ID NO: 331

anti-IL17R-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 335

(brodalumab)
light chain = SEQ ID NO: 326

anti-IL17R-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 335

(brodalumab)
light chain = SEQ ID NO: 327

anti-IL17R-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 335

(brodalumab)
light chain = SEQ ID NO: 328

anti-IL17R-TIM3ecd
heavy chain = SEQ ID NO: 335

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL17R-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 336

(brodalumab)
light chain = SEQ ID NO: 331

anti-IL17R-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 336

(brodalumab)
light chain = SEQ ID NO: 326

anti-IL17R-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 336

(brodalumab)
light chain = SEQ ID NO: 327

anti-IL17R-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 336

(brodalumab)
light chain = SEQ ID NO: 328

anti-IL17R-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 336

(brodalumab)
light chain = SEQ ID NO: 329

anti-IL17R-VEGFRecd
heavy chain = SEQ ID NO: 336

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL23-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 337

(risankizumab)
light chain = SEQ ID NO: 338

anti-IL23-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 337

(risankizumab)
light chain = SEQ ID NO: 339

anti-IL23-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 337

(risankizumab)
light chain = SEQ ID NO: 340

anti-IL23-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 337

(risankizumab)
light chain = SEQ ID NO: 341

anti-IL23-BTLAecd
heavy chain = SEQ ID NO: 337

(risankizumab)
light chain = SEQ ID NO: 75

anti-IL23-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 342

(risankizumab)
light chain = SEQ ID NO: 343

anti-IL23-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 342

(risankizumab)
light chain = SEQ ID NO: 339

anti-IL23-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 342

(risankizumab)
light chain = SEQ ID NO: 340

anti-IL23-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 342

(risankizumab)
light chain = SEQ ID NO: 341

anti-IL23-PD1ecd
heavy chain = SEQ ID NO: 342

(risankizumab)
light chain = SEQ ID NO: 75

anti-IL23-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 344

(risankizumab)
light chain = SEQ ID NO: 343

anti-IL23-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 344

(risankizumab)
light chain = SEQ ID NO: 338

anti-IL23-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 344

(risankizumab)
light chain = SEQ ID NO: 340

anti-IL23-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 344

(risankizumab)
light chain = SEQ ID NO: 341

anti-IL23-SIGLEC10ecd
heavy chain = SEQ ID NO: 344

(risankizumab)
light chain = SEQ ID NO: 75

anti-IL23-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 345

(risankizumab)
light chain = SEQ ID NO: 343

anti-IL23-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 345

(risankizumab)
light chain = SEQ ID NO: 338

anti-IL23-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 345

(risankizumab)
light chain = SEQ ID NO: 339

anti-IL23-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 345

(risankizumab)
light chain = SEQ ID NO: 341

anti-IL23-SIRPaecd
heavy chain = SEQ ID NO: 345

(risankizumab)
light chain = SEQ ID NO: 75

anti-IL23-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 346

(risankizumab)
light chain = SEQ ID NO: 343

anti-IL23-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 346

(risankizumab)
light chain = SEQ ID NO: 338

anti-IL23-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 346

(risankizumab)
light chain = SEQ ID NO: 339

anti-IL23-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 346

(risankizumab)
light chain = SEQ ID NO: 340

anti-IL23-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 346

(risankizumab)
light chain = SEQ ID NO: 341

anti-IL23-TGFbRecd
heavy chain = SEQ ID NO: 346

(risankizumab)
light chain = SEQ ID NO: 75

anti-IL23-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 347

(risankizumab)
light chain = SEQ ID NO: 343

anti-IL23-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 347

(risankizumab)
light chain = SEQ ID NO: 338

anti-IL23-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 347

(risankizumab)
light chain = SEQ ID NO: 339

anti-IL23-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 347

(risankizumab)
light chain = SEQ ID NO: 340

anti-IL23-TIM3ecd
heavy chain = SEQ ID NO: 347

(risankizumab)
light chain = SEQ ID NO: 75

anti-IL23-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 348

(risankizumab)
light chain = SEQ ID NO: 343

anti-IL23-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 348

(risankizumab)
light chain = SEQ ID NO: 338

anti-IL23-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 348

(risankizumab)
light chain = SEQ ID NO: 339

anti-IL23-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 348

(risankizumab)
light chain = SEQ ID NO: 340

anti-IL23-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 348

(risankizumab)
light chain = SEQ ID NO: 341

anti-IL23-VEGFRecd
heavy chain = SEQ ID NO: 348

(risankizumab)
light chain = SEQ ID NO: 75

anti-IL1b-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 349

(canakinumab)
light chain = SEQ ID NO: 350

anti-IL1b-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 349

(canakinumab)
light chain = SEQ ID NO: 351

anti-IL1b-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 349

(canakinumab)
light chain = SEQ ID NO: 352

anti-IL1b-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 349

(canakinumab)
light chain = SEQ ID NO: 353

anti-IL1b-BTLAecd
heavy chain = SEQ ID NO: 349

(canakinumab)
light chain = SEQ ID NO: 69

anti-IL1b-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 354

(canakinumab)
light chain = SEQ ID NO: 355

anti-IL1b-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 354

(canakinumab)
light chain = SEQ ID NO: 351

anti-IL1b-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 354

(canakinumab)
light chain = SEQ ID NO: 352

anti-IL1b-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 354

(canakinumab)
light chain = SEQ ID NO: 353

anti-IL1b-PD1ecd
heavy chain = SEQ ID NO: 354

(canakinumab)
light chain = SEQ ID NO: 69

anti-IL1b-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 356

(canakinumab)
light chain = SEQ ID NO: 355

anti-IL1b-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 356

(canakinumab)
light chain = SEQ ID NO: 350

anti-IL1b-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 356

(canakinumab)
light chain = SEQ ID NO: 352

anti-IL1b-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 356

(canakinumab)
light chain = SEQ ID NO: 353

anti-IL1b-SIGLEC10ecd
heavy chain = SEQ ID NO: 356

(canakinumab)
light chain = SEQ ID NO: 69

anti-IL1b-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 357

(canakinumab)
light chain = SEQ ID NO: 355

anti-IL1b-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 357

(canakinumab)
light chain = SEQ ID NO: 350

anti-IL1b-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 357

(canakinumab)
light chain = SEQ ID NO: 351

anti-IL1b-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 357

(canakinumab)
light chain = SEQ ID NO: 353

anti-IL1b-SIRPaecd
heavy chain = SEQ ID NO: 357

(canakinumab)
light chain = SEQ ID NO: 69

anti-IL1b-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 358

(canakinumab)
light chain = SEQ ID NO: 355

anti-IL1b-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 358

(canakinumab)
light chain = SEQ ID NO: 350

anti-IL1b-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 358

(canakinumab)
light chain = SEQ ID NO: 351

anti-IL1b-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 358

(canakinumab)
light chain = SEQ ID NO: 352

anti-IL1b-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 358

(canakinumab)
light chain = SEQ ID NO: 353

anti-IL1b-TGFbRecd
heavy chain = SEQ ID NO: 358

(canakinumab)
light chain = SEQ ID NO: 69

anti-IL1b-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 359

(canakinumab)
light chain = SEQ ID NO: 355

anti-IL1b-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 359

(canakinumab)
light chain = SEQ ID NO: 350

anti-IL1b-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 359

(canakinumab)
light chain = SEQ ID NO: 351

anti-IL1b-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 359

(canakinumab)
light chain = SEQ ID NO: 352

anti-IL1b-TIM3ecd
heavy chain = SEQ ID NO: 359

(canakinumab)
light chain = SEQ ID NO: 69

anti-IL1b-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 360

(canakinumab)
light chain = SEQ ID NO: 355

anti-IL1b-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 360

(canakinumab)
light chain = SEQ ID NO: 350

anti-IL1b-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 360

(canakinumab)
light chain = SEQ ID NO: 351

anti-IL1b-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 360

(canakinumab)
light chain = SEQ ID NO: 352

anti-IL1b-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 360

(canakinumab)
light chain = SEQ ID NO: 353

anti-IL1b-VEGFRecd
heavy chain = SEQ ID NO: 360

(canakinumab)
light chain = SEQ ID NO: 69

anti-VEGF-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 361

(bevacizumab)
light chain = SEQ ID NO: 362

anti-VEGF-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 361

(bevacizumab)
light chain = SEQ ID NO: 363

anti-VEGF-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 361

(bevacizumab)
light chain = SEQ ID NO: 364

anti-VEGF-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 361

(bevacizumab)
light chain = SEQ ID NO: 365

anti-VEGF-BTLAecd
heavy chain = SEQ ID NO: 361

(bevacizumab)
light chain = SEQ ID NO: 32

anti-VEGF-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 366

(bevacizumab)
light chain = SEQ ID NO: 367

anti-VEGF-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 366

(bevacizumab)
light chain = SEQ ID NO: 363

anti-VEGF-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 366

(bevacizumab)
light chain = SEQ ID NO: 364

anti-VEGF-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 366

(bevacizumab)
light chain = SEQ ID NO: 365

anti-VEGF-PD1ecd
heavy chain = SEQ ID NO: 366

(bevacizumab)
light chain = SEQ ID NO: 32

anti-VEGF-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 368

(bevacizumab)
light chain = SEQ ID NO: 367

anti-VEGF-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 368

(bevacizumab)
light chain = SEQ ID NO: 362

anti-VEGF-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 368

(bevacizumab)
light chain = SEQ ID NO: 364

anti-VEGF-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 368

(bevacizumab)
light chain = SEQ ID NO: 365

anti-VEGF-SIGLEC10ecd
heavy chain = SEQ ID NO: 368

(bevacizumab)
light chain = SEQ ID NO: 32

anti-VEGF-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 369

(bevacizumab)
light chain = SEQ ID NO: 367

anti-VEGF-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 369

(bevacizumab)
light chain = SEQ ID NO: 362

anti-VEGF-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 369

(bevacizumab)
light chain = SEQ ID NO: 363

anti-VEGF-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 369

(bevacizumab)
light chain = SEQ ID NO: 365

anti-VEGF-SIRPaecd
heavy chain = SEQ ID NO: 369

(bevacizumab)
light chain = SEQ ID NO: 32

anti-VEGF-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 370

(bevacizumab)
light chain = SEQ ID NO: 367

anti-VEGF-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 370

(bevacizumab)
light chain = SEQ ID NO: 362

anti-VEGF-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 370

(bevacizumab)
light chain = SEQ ID NO: 363

anti-VEGF-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 370

(bevacizumab)
light chain = SEQ ID NO: 364

anti-VEGF-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 370

(bevacizumab)
light chain = SEQ ID NO: 365

anti-VEGF-TGFbRecd
heavy chain = SEQ ID NO: 370

(bevacizumab)
light chain = SEQ ID NO: 32

anti-VEGF-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 371

(bevacizumab)
light chain = SEQ ID NO: 367

anti-VEGF-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 371

(bevacizumab)
light chain = SEQ ID NO: 362

anti-VEGF-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 371

(bevacizumab)
light chain = SEQ ID NO: 363

anti-VEGF-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 371

(bevacizumab)
light chain = SEQ ID NO: 364

anti-VEGF-TIM3ecd
heavy chain = SEQ ID NO: 371

(bevacizumab)
light chain = SEQ ID NO: 32

anti-VEGFR-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 372

(ramucirumab)
light chain = SEQ ID NO: 373

anti-VEGFR-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 372

(ramucirumab)
light chain = SEQ ID NO: 374

anti-VEGFR-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 372

(ramucirumab)
light chain = SEQ ID NO: 375

anti-VEGFR-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 372

(ramucirumab)
light chain = SEQ ID NO: 376

anti-VEGFR-BTLAecd
heavy chain = SEQ ID NO: 372

(ramucirumab)
light chain = SEQ ID NO: 148

anti-VEGFR-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 377

(ramucirumab)
light chain = SEQ ID NO: 378

anti-VEGFR-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 377

(ramucirumab)
light chain = SEQ ID NO: 374

anti-VEGFR-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 377

(ramucirumab)
light chain = SEQ ID NO: 375

anti-VEGFR-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 377

(ramucirumab)
light chain = SEQ ID NO: 376

anti-VEGFR-PD1ecd
heavy chain = SEQ ID NO: 377

(ramucirumab)
light chain = SEQ ID NO: 148

anti-VEGFR-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 379

(ramucirumab)
light chain = SEQ ID NO: 378

anti-VEGFR-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 379

(ramucirumab)
light chain = SEQ ID NO: 373

anti-VEGFR-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 379

(ramucirumab)
light chain = SEQ ID NO: 375

anti-VEGFR-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 379

(ramucirumab)
light chain = SEQ ID NO: 376

anti-VEGFR-SIGLEC10ecd
heavy chain = SEQ ID NO: 379

(ramucirumab)
light chain = SEQ ID NO: 148

anti-VEGFR-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 380

(ramucirumab)
light chain = SEQ ID NO: 378

anti-VEGFR-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 380

(ramucirumab)
light chain = SEQ ID NO: 373

anti-VEGFR-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 380

(ramucirumab)
light chain = SEQ ID NO: 374

anti-VEGFR-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 380

(ramucirumab)
light chain = SEQ ID NO: 376

anti-VEGFR-SIRPaecd
heavy chain = SEQ ID NO: 380

(ramucirumab)
light chain = SEQ ID NO: 148

anti-VEGFR-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 381

(ramucirumab)
light chain = SEQ ID NO: 378

anti-VEGFR-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 381

(ramucirumab)
light chain = SEQ ID NO: 373

anti-VEGFR-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 381

(ramucirumab)
light chain = SEQ ID NO: 374

anti-VEGFR-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 381

(ramucirumab)
light chain = SEQ ID NO: 375

anti-VEGFR-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 381

(ramucirumab)
light chain = SEQ ID NO: 376

anti-VEGFR-TGFbRecd
heavy chain = SEQ ID NO: 381

(ramucirumab)
light chain = SEQ ID NO: 148

anti-VEGFR-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 382

(ramucirumab)
light chain = SEQ ID NO: 378

anti-VEGFR-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 382

(ramucirumab)
light chain = SEQ ID NO: 373

anti-VEGFR-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 382

(ramucirumab)
light chain = SEQ ID NO: 374

anti-VEGFR-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 382

(ramucirumab)
light chain = SEQ ID NO: 375

anti-VEGFR-TIM3ecd
heavy chain = SEQ ID NO: 382

(ramucirumab)
light chain = SEQ ID NO: 148

anti-CD47-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 383

(5F9)
light chain = SEQ ID NO: 384

anti-CD47-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 383

(5F9)
light chain = SEQ ID NO: 385

anti-CD47-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 383

(5F9)
light chain = SEQ ID NO: 386

anti-CD47-BTLAecd
heavy chain = SEQ ID NO: 383

(5F9)
light chain = SEQ ID NO: 22

anti-CD47-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 387

(5F9)
light chain = SEQ ID NO: 388

anti-CD47-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 387

(5F9)
light chain = SEQ ID NO: 385

anti-CD47-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 387

(5F9)
light chain = SEQ ID NO: 386

anti-CD47-PD1ecd
heavy chain = SEQ ID NO: 387

(5F9)
light chain = SEQ ID NO: 22

anti-CD47-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 389

(5F9)
light chain = SEQ ID NO: 388

anti-CD47-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 389

(5F9)
light chain = SEQ ID NO: 384

anti-CD47-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 389

(5F9)
light chain = SEQ ID NO: 386

anti-CD47-SIGLEC10ecd
heavy chain = SEQ ID NO: 389

(5F9)
light chain = SEQ ID NO: 22

anti-CD47-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 390

(5F9)
light chain = SEQ ID NO: 388

anti-CD47-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 390

(5F9)
light chain = SEQ ID NO: 384

anti-CD47-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 390

(5F9)
light chain = SEQ ID NO: 385

anti-CD47-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 390

(5F9)
light chain = SEQ ID NO: 386

anti-CD47-TGFbRecd
heavy chain = SEQ ID NO: 390

(5F9)
light chain = SEQ ID NO: 22

anti-CD47-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 391

(5F9)
light chain = SEQ ID NO: 388

anti-CD47-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 391

(5F9)
light chain = SEQ ID NO: 384

anti-CD47-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 391

(5F9)
light chain = SEQ ID NO: 385

anti-CD47-TIM3ecd
heavy chain = SEQ ID NO: 391

(5F9)
light chain = SEQ ID NO: 22

anti-CD47-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 392

(5F9)
light chain = SEQ ID NO: 388

anti-CD47-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 392

(5F9)
light chain = SEQ ID NO: 384

anti-CD47-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 392

(5F9)
light chain = SEQ ID NO: 385

anti-CD47-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 392

(5F9)
light chain = SEQ ID NO: 386

anti-CD47-VEGFRecd
heavy chain = SEQ ID NO: 392

(5F9)
light chain = SEQ ID NO: 22

anti-TGFb-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 393

(fresolimumab)
light chain = SEQ ID NO: 394

anti-TGFb-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 393

(fresolimumab)
light chain = SEQ ID NO: 395

anti-TGFb-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 393

(fresolimumab)
light chain = SEQ ID NO: 396

anti-TGFb-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 393

(fresolimumab)
light chain = SEQ ID NO: 397

anti-TGFb-BTLAecd
heavy chain = SEQ ID NO: 393

(fresolimumab)
light chain = SEQ ID NO: 133

anti-TGFb-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 398

(fresolimumab)
light chain = SEQ ID NO: 399

anti-TGFb-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 398

(fresolimumab)
light chain = SEQ ID NO: 395

anti-TGFb-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 398

(fresolimumab)
light chain = SEQ ID NO: 396

anti-TGFb-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 398

(fresolimumab)
light chain = SEQ ID NO: 397

anti-TGFb-PD1ecd
heavy chain = SEQ ID NO: 398

(fresolimumab)
light chain = SEQ ID NO: 133

anti-TGFb-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 400

(fresolimumab)
light chain = SEQ ID NO: 399

anti-TGFb-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 400

(fresolimumab)
light chain = SEQ ID NO: 394

anti-TGFb-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 400

(fresolimumab)
light chain = SEQ ID NO: 396

anti-TGFb-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 400

(fresolimumab)
light chain = SEQ ID NO: 397

anti-TGFb-SIGLEC10ecd
heavy chain = SEQ ID NO: 400

(fresolimumab)
light chain = SEQ ID NO: 133

anti-TGFb-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 401

(fresolimumab)
light chain = SEQ ID NO: 399

anti-TGFb-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 401

(fresolimumab)
light chain = SEQ ID NO: 394

anti-TGFb-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 401

(fresolimumab)
light chain = SEQ ID NO: 395

anti-TGFb-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 401

(fresolimumab)
light chain = SEQ ID NO: 397

anti-TGFb-SIRPaecd
heavy chain = SEQ ID NO: 401

(fresolimumab)
light chain = SEQ ID NO: 133

anti-TGFb-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 402

(fresolimumab)
light chain = SEQ ID NO: 399

anti-TGFb-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 402

(fresolimumab)
light chain = SEQ ID NO: 394

anti-TGFb-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 402

(fresolimumab)
light chain = SEQ ID NO: 395

anti-TGFb-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 402

(fresolimumab)
light chain = SEQ ID NO: 396

anti-TGFb-TIM3ecd
heavy chain = SEQ ID NO: 402

(fresolimumab)
light chain = SEQ ID NO: 133

anti-TGFb-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 403

(fresolimumab)
light chain = SEQ ID NO: 399

anti-TGFb-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 403

(fresolimumab)
light chain = SEQ ID NO: 394

anti-TGFb-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 403

(fresolimumab)
light chain = SEQ ID NO: 395

anti-TGFb-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 403

(fresolimumab)
light chain = SEQ ID NO: 396

anti-TGFb-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 403

(fresolimumab)
light chain = SEQ ID NO: 397

anti-TGFb-VEGFRecd
heavy chain = SEQ ID NO: 403

(fresolimumab)
light chain = SEQ ID NO: 133

anti-LAP-BTLAecd
heavy chain = SEQ ID NO: 404

(7H4)
light chain = SEQ ID NO: 81

anti-LAP-PD1ecd
heavy chain = SEQ ID NO: 405

(7H4)
light chain = SEQ ID NO: 81

anti-LAP-SIGLEC10ecd
heavy chain = SEQ ID NO: 406

(7H4)
light chain = SEQ ID NO: 81

anti-LAP-SIRPaecd
heavy chain = SEQ ID NO: 407

(7H4)
light chain = SEQ ID NO: 81

anti-LAP-TIM3ecd
heavy chain = SEQ ID NO: 408

(7H4)
light chain = SEQ ID NO: 81

anti-LAP-VEGFRecd
heavy chain = SEQ ID NO: 409

(7H4)
light chain = SEQ ID NO: 81

anti-GARP-BTLAecd
heavy chain = SEQ ID NO: 410

(ARGX-115)
light chain = SEQ ID NO: 49

anti-GARP-PD1ecd
heavy chain = SEQ ID NO: 411

(ARGX-115)
light chain = SEQ ID NO: 49

anti-GARP-SIGLEC10ecd
heavy chain = SEQ ID NO: 412

(ARGX-115)
light chain = SEQ ID NO: 49

anti-GARP-SIRPaecd
heavy chain = SEQ ID NO: 413

(ARGX-115)
light chain = SEQ ID NO: 49

anti-GARP-TIM3ecd
heavy chain = SEQ ID NO: 414

(ARGX-115)
light chain = SEQ ID NO: 49

anti-GARP-VEGFRecd
heavy chain = SEQ ID NO: 415

(ARGX-115)
light chain = SEQ ID NO: 49

anti-CD73-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 416

(GS1423)
light chain = SEQ ID NO: 417

anti-CD73-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 416

(GS1423)
light chain = SEQ ID NO: 418

anti-CD73-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 416

(GS1423)
light chain = SEQ ID NO: 419

anti-CD73-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 416

(GS1423)
light chain = SEQ ID NO: 420

anti-CD73-BTLAecd
heavy chain = SEQ ID NO: 416

(GS1423)
light chain = SEQ ID NO: 24

anti-CD73-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 421

(GS1423)
light chain = SEQ ID NO: 422

anti-CD73-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 421

(GS1423)
light chain = SEQ ID NO: 418

anti-CD73-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 421

(GS1423)
light chain = SEQ ID NO: 419

anti-CD73-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 421

(GS1423)
light chain = SEQ ID NO: 420

anti-CD73-PD1ecd
heavy chain = SEQ ID NO: 421

(GS1423)
light chain = SEQ ID NO: 24

anti-CD73-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 423

(GS1423)
light chain = SEQ ID NO: 422

anti-CD73-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 423

(GS1423)
light chain = SEQ ID NO: 417

anti-CD73-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 423

(GS1423)
light chain = SEQ ID NO: 419

anti-CD73-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 423

(GS1423)
light chain = SEQ ID NO: 420

anti-CD73-SIGLEC10ecd
heavy chain = SEQ ID NO: 423

(GS1423)
light chain = SEQ ID NO: 24

anti-CD73-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 424

(GS1423)
light chain = SEQ ID NO: 422

anti-CD73-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 424

(GS1423)
light chain = SEQ ID NO: 417

anti-CD73-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 424

(GS1423)
light chain = SEQ ID NO: 418

anti-CD73-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 424

(GS1423)
light chain = SEQ ID NO: 420

anti-CD73-SIRPaecd
heavy chain = SEQ ID NO: 424

(GS1423)
light chain = SEQ ID NO: 24

anti-CD73-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 425

(GS1423)
light chain = SEQ ID NO: 422

anti-CD73-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 425

(GS1423)
light chain = SEQ ID NO: 417

anti-CD73-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 425

(GS1423)
light chain = SEQ ID NO: 418

anti-CD73-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 425

(GS1423)
light chain = SEQ ID NO: 419

anti-CD73-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 425

(GS1423)
light chain = SEQ ID NO: 420

anti-CD73-TGFbRecd
heavy chain = SEQ ID NO: 425

(GS1423)
light chain = SEQ ID NO: 24

anti-CD73-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 426

(GS1423)
light chain = SEQ ID NO: 422

anti-CD73-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 426

(GS1423)
light chain = SEQ ID NO: 417

anti-CD73-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 426

(GS1423)
light chain = SEQ ID NO: 418

anti-CD73-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 426

(GS1423)
light chain = SEQ ID NO: 419

anti-CD73-TIM3ecd
heavy chain = SEQ ID NO: 426

(GS1423)
light chain = SEQ ID NO: 24

anti-CD73-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 427

(GS1423)
light chain = SEQ ID NO: 422

anti-CD73-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 427

(GS1423)
light chain = SEQ ID NO: 417

anti-CD73-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 427

(GS1423)
light chain = SEQ ID NO: 418

anti-CD73-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 427

(GS1423)
light chain = SEQ ID NO: 419

anti-CD73-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 427

(GS1423)
light chain = SEQ ID NO: 420

anti-CD73-VEGFRecd
heavy chain = SEQ ID NO: 427

(GS1423)
light chain = SEQ ID NO: 24

anti-CD39-BTLAecd
heavy chain = SEQ ID NO: 428

(IPH5201)
light chain = SEQ ID NO: 18

anti-CD39-PD1ecd
heavy chain = SEQ ID NO: 429

(IPH5201)
light chain = SEQ ID NO: 18

anti-CD39-SIGLEC10ecd
heavy chain = SEQ ID NO: 430

(IPH5201)
light chain = SEQ ID NO: 18

anti-CD39-SIRPaecd
heavy chain = SEQ ID NO: 431

(IPH5201)
light chain = SEQ ID NO: 18

anti-CD39-TGFbRecd
heavy chain = SEQ ID NO: 432

(IPH5201)
light chain = SEQ ID NO: 18

anti-CD39-TIM3ecd
heavy chain = SEQ ID NO: 433

(IPH5201)
light chain = SEQ ID NO: 18

anti-CD39-VEGFRecd
heavy chain = SEQ ID NO: 434

(IPH5201)
light chain = SEQ ID NO: 18

anti-CTLA4-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 435

(ipilimumab)
light chain = SEQ ID NO: 436

anti-CTLA4-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 435

(ipilimumab)
light chain = SEQ ID NO: 437

anti-CTLA4-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 435

(ipilimumab)
light chain = SEQ ID NO: 438

anti-CTLA4-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 435

(ipilimumab)
light chain = SEQ ID NO: 439

anti-CTLA4-BTLAecd
heavy chain = SEQ ID NO: 435

(ipilimumab)
light chain = SEQ ID NO: 28

anti-CTLA4-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 440

(ipilimumab)
light chain = SEQ ID NO: 441

anti-CTLA4-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 440

(ipilimumab)
light chain = SEQ ID NO: 437

anti-CTLA4-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 440

(ipilimumab)
light chain = SEQ ID NO: 438

anti-CTLA4-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 440

(ipilimumab)
light chain = SEQ ID NO: 439

anti-CTLA4-PD1ecd
heavy chain = SEQ ID NO: 440

(ipilimumab)
light chain = SEQ ID NO: 28

anti-CTLA4-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 442

(ipilimumab)
light chain = SEQ ID NO: 441

anti-CTLA4-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 442

(ipilimumab)
light chain = SEQ ID NO: 436

anti-CTLA4-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 442

(ipilimumab)
light chain = SEQ ID NO: 438

anti-CTLA4-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 442

(ipilimumab)
light chain = SEQ ID NO: 439

anti-CTLA4-SIGLEC10ecd
heavy chain = SEQ ID NO: 442

(ipilimumab)
light chain = SEQ ID NO: 28

anti-CTLA4-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 443

(ipilimumab)
light chain = SEQ ID NO: 441

anti-CTLA4-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 443

(ipilimumab)
light chain = SEQ ID NO: 436

anti-CTLA4-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 443

(ipilimumab)
light chain = SEQ ID NO: 437

anti-CTLA4-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 443

(ipilimumab)
light chain = SEQ ID NO: 439

anti-CTLA4-SIRPaecd
heavy chain = SEQ ID NO: 443

(ipilimumab)
light chain = SEQ ID NO: 28

anti-CTLA4-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 444

(ipilimumab)
light chain = SEQ ID NO: 441

anti-CTLA4-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 444

(ipilimumab)
light chain = SEQ ID NO: 436

anti-CTLA4-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 444

(ipilimumab)
light chain = SEQ ID NO: 437

anti-CTLA4-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 444

(ipilimumab)
light chain = SEQ ID NO: 438

anti-CTLA4-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 444

(ipilimumab)
light chain = SEQ ID NO: 439

anti-CTLA4-TGFbRecd
heavy chain = SEQ ID NO: 444

(ipilimumab)
light chain = SEQ ID NO: 28

anti-CTLA4-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 445

(ipilimumab)
light chain = SEQ ID NO: 441

anti-CTLA4-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 445

(ipilimumab)
light chain = SEQ ID NO: 436

anti-CTLA4-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 445

(ipilimumab)
light chain = SEQ ID NO: 437

anti-CTLA4-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 445

(ipilimumab)
light chain = SEQ ID NO: 438

anti-CTLA4-TIM3ecd
heavy chain = SEQ ID NO: 445

(ipilimumab)
light chain = SEQ ID NO: 28

anti-CTLA4-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 446

(ipilimumab)
light chain = SEQ ID NO: 441

anti-CTLA4-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 446

(ipilimumab)
light chain = SEQ ID NO: 436

anti-CTLA4-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 446

(ipilimumab)
light chain = SEQ ID NO: 437

anti-CTLA4-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 446

(ipilimumab)
light chain = SEQ ID NO: 438

anti-CTLA4-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 446

(ipilimumab)
light chain = SEQ ID NO: 439

anti-CTLA4-VEGFRecd
heavy chain = SEQ ID NO: 446

(ipilimumab)
light chain = SEQ ID NO: 28

anti-PD1-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 447

(pembrolizumab)
light chain = SEQ ID NO: 448

anti-PD1-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 447

(pembrolizumab)
light chain = SEQ ID NO: 449

anti-PD1-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 447

(pembrolizumab)
light chain = SEQ ID NO: 450

anti-PD1-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 447

(pembrolizumab)
light chain = SEQ ID NO: 451

anti-PD1-BTLAecd
heavy chain = SEQ ID NO: 447

(pembrolizumab)
light chain = SEQ ID NO: 101

anti-PD1-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 452

(pembrolizumab)
light chain = SEQ ID NO: 453

anti-PD1-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 452

(pembrolizumab)
light chain = SEQ ID NO: 449

anti-PD1-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 452

(pembrolizumab)
light chain = SEQ ID NO: 450

anti-PD1-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 452

(pembrolizumab)
light chain = SEQ ID NO: 451

anti-PD1-PD1ecd
heavy chain = SEQ ID NO: 452

(pembrolizumab)
light chain = SEQ ID NO: 101

anti-PD1-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 454

(pembrolizumab)
light chain = SEQ ID NO: 453

anti-PD1-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 454

(pembrolizumab)
light chain = SEQ ID NO: 448

anti-PD1-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 454

(pembrolizumab)
light chain = SEQ ID NO: 450

anti-PD1-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 454

(pembrolizumab)
light chain = SEQ ID NO: 451

anti-PD1-SIGLEC10ecd
heavy chain = SEQ ID NO: 454

(pembrolizumab)
light chain = SEQ ID NO: 101

anti-PD1-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 455

(pembrolizumab)
light chain = SEQ ID NO: 453

anti-PD1-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 455

(pembrolizumab)
light chain = SEQ ID NO: 448

anti-PD1-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 455

(pembrolizumab)
light chain = SEQ ID NO: 449

anti-PD1-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 455

(pembrolizumab)
light chain = SEQ ID NO: 451

anti-PD1-SIRPaecd
heavy chain = SEQ ID NO: 455

(pembrolizumab)
light chain = SEQ ID NO: 101

anti-PD1-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 456

(pembrolizumab)
light chain = SEQ ID NO: 453

anti-PD1-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 456

(pembrolizumab)
light chain = SEQ ID NO: 448

anti-PD1-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 456

(pembrolizumab)
light chain = SEQ ID NO: 449

anti-PD1-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 456

(pembrolizumab)
light chain = SEQ ID NO: 450

anti-PD1-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 456

(pembrolizumab)
light chain = SEQ ID NO: 451

anti-PD1-TGFbRecd
heavy chain = SEQ ID NO: 456

(pembrolizumab)
light chain = SEQ ID NO: 101

anti-PD1-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 457

(pembrolizumab)
light chain = SEQ ID NO: 453

anti-PD1-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 457

(pembrolizumab)
light chain = SEQ ID NO: 448

anti-PD1-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 457

(pembrolizumab)
light chain = SEQ ID NO: 449

anti-PD1-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 457

(pembrolizumab)
light chain = SEQ ID NO: 450

anti-PD1-TIM3ecd
heavy chain = SEQ ID NO: 457

(pembrolizumab)
light chain = SEQ ID NO: 101

anti-PD1-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 458

(pembrolizumab)
light chain = SEQ ID NO: 453

anti-PD1-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 458

(pembrolizumab)
light chain = SEQ ID NO: 448

anti-PD1-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 458

(pembrolizumab)
light chain = SEQ ID NO: 449

anti-PD1-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 458

(pembrolizumab)
light chain = SEQ ID NO: 450

anti-PD1-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 458

(pembrolizumab)
light chain = SEQ ID NO: 451

anti-PD1-VEGFRecd
heavy chain = SEQ ID NO: 458

(pembrolizumab)
light chain = SEQ ID NO: 101

anti-PDL1-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 459

(atezolizumab)
light chain = SEQ ID NO: 460

anti-PDL1-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 459

(atezolizumab)
light chain = SEQ ID NO: 461

anti-PDL1-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 459

(atezolizumab)
light chain = SEQ ID NO: 462

anti-PDL1-BTLAecd
heavy chain = SEQ ID NO: 459

(atezolizumab)
light chain = SEQ ID NO: 109

anti-PDL1-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 463

(atezolizumab)
light chain = SEQ ID NO: 464

anti-PDL1-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 463

(atezolizumab)
light chain = SEQ ID NO: 461

anti-PDL1-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 463

(atezolizumab)
light chain = SEQ ID NO: 462

anti-PDL1-SIGLEC10ecd
heavy chain = SEQ ID NO: 463

(atezolizumab)
light chain = SEQ ID NO: 109

anti-PDL1-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 465

(atezolizumab)
light chain = SEQ ID NO: 464

anti-PDL1-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 465

(atezolizumab)
light chain = SEQ ID NO: 460

anti-PDL1-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 465

(atezolizumab)
light chain = SEQ ID NO: 462

anti-PDL1-SIRPaecd
heavy chain = SEQ ID NO: 465

(atezolizumab)
light chain = SEQ ID NO: 109

anti-PDL1-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 466

(atezolizumab)
light chain = SEQ ID NO: 464

anti-PDL1-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 466

(atezolizumab)
light chain = SEQ ID NO: 460

anti-PDL1-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 466

(atezolizumab)
light chain = SEQ ID NO: 461

anti-PDL1-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 466

(atezolizumab)
light chain = SEQ ID NO: 462

anti-PDL1-TGFbRecd
heavy chain = SEQ ID NO: 466

(atezolizumab)
light chain = SEQ ID NO: 109

anti-PDL1-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 467

(atezolizumab)
light chain = SEQ ID NO: 464

anti-PDL1-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 467

(atezolizumab)
light chain = SEQ ID NO: 460

anti-PDL1-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 467

(atezolizumab)
light chain = SEQ ID NO: 461

anti-PDL1-TIM3ecd
heavy chain = SEQ ID NO: 467

(atezolizumab)
light chain = SEQ ID NO: 109

anti-PDL1-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 468

(atezolizumab)
light chain = SEQ ID NO: 464

anti-PDL1-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 468

(atezolizumab)
light chain = SEQ ID NO: 460

anti-PDL1-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 468

(atezolizumab)
light chain = SEQ ID NO: 461

anti-PDL1-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 468

(atezolizumab)
light chain = SEQ ID NO: 462

anti-PDL1-VEGFRecd
heavy chain = SEQ ID NO: 468

(atezolizumab)
light chain = SEQ ID NO: 109

anti-TIGIT-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 469

(tiragolumab)
light chain = SEQ ID NO: 470

anti-TIGIT-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 469

(tiragolumab)
light chain = SEQ ID NO: 471

anti-TIGIT-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 469

(tiragolumab)
light chain = SEQ ID NO: 472

anti-TIGIT-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 469

(tiragolumab)
light chain = SEQ ID NO: 473

anti-TIGIT-BTLAecd
heavy chain = SEQ ID NO: 469

(tiragolumab)
light chain = SEQ ID NO: 139

anti-TIGIT-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 474

(tiragolumab)
light chain = SEQ ID NO: 475

anti-TIGIT-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 474

(tiragolumab)
light chain = SEQ ID NO: 471

anti-TIGIT-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 474

(tiragolumab)
light chain = SEQ ID NO: 472

anti-TIGIT-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 474

(tiragolumab)
light chain = SEQ ID NO: 473

anti-TIGIT-PD1ecd
heavy chain = SEQ ID NO: 474

(tiragolumab)
light chain = SEQ ID NO: 139

anti-TIGIT-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 476

(tiragolumab)
light chain = SEQ ID NO: 475

anti-TIGIT-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 476

(tiragolumab)
light chain = SEQ ID NO: 470

anti-TIGIT-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 476

(tiragolumab)
light chain = SEQ ID NO: 472

anti-TIGIT-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 476

(tiragolumab)
light chain = SEQ ID NO: 473

anti-TIGIT-SIGLEC10ecd
heavy chain = SEQ ID NO: 476

(tiragolumab)
light chain = SEQ ID NO: 139

anti-TIGIT-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 477

(tiragolumab)
light chain = SEQ ID NO: 475

anti-TIGIT-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 477

(tiragolumab)
light chain = SEQ ID NO: 470

anti-TIGIT-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 477

(tiragolumab)
light chain = SEQ ID NO: 471

anti-TIGIT-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 477

(tiragolumab)
light chain = SEQ ID NO: 473

anti-TIGIT-SIRPaecd
heavy chain = SEQ ID NO: 477

(tiragolumab)
light chain = SEQ ID NO: 139

anti-TIGIT-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 478

(tiragolumab)
light chain = SEQ ID NO: 475

anti-TIGIT-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 478

(tiragolumab)
light chain = SEQ ID NO: 470

anti-TIGIT-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 478

(tiragolumab)
light chain = SEQ ID NO: 471

anti-TIGIT-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 478

(tiragolumab)
light chain = SEQ ID NO: 472

anti-TIGIT-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 478

(tiragolumab)
light chain = SEQ ID NO: 473

anti-TIGIT-TGFbRecd
heavy chain = SEQ ID NO: 478

(tiragolumab)
light chain = SEQ ID NO: 139

anti-TIGIT-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 479

(tiragolumab)
light chain = SEQ ID NO: 475

anti-TIGIT-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 479

(tiragolumab)
light chain = SEQ ID NO: 470

anti-TIGIT-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 479

(tiragolumab)
light chain = SEQ ID NO: 471

anti-TIGIT-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 479

(tiragolumab)
light chain = SEQ ID NO: 472

anti-TIGIT-TIM3ecd
heavy chain = SEQ ID NO: 479

(tiragolumab)
light chain = SEQ ID NO: 139

anti-TIGIT-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 480

(tiragolumab)
light chain = SEQ ID NO: 475

anti-TIGIT-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 480

(tiragolumab)
light chain = SEQ ID NO: 470

anti-TIGIT-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 480

(tiragolumab)
light chain = SEQ ID NO: 471

anti-TIGIT-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 480

(tiragolumab)
light chain = SEQ ID NO: 472

anti-TIGIT-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 480

(tiragolumab)
light chain = SEQ ID NO: 473

anti-TIGIT-VEGFRecd
heavy chain = SEQ ID NO: 480

(tiragolumab)
light chain = SEQ ID NO: 139

anti-TIM3-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 481

(M6903)
light chain = SEQ ID NO: 482

anti-TIM3-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 481

(M6903)
light chain = SEQ ID NO: 483

anti-TIM3-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 481

(M6903)
light chain = SEQ ID NO: 484

anti-TIM3-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 481

(M6903)
light chain = SEQ ID NO: 485

anti-TIM3-BTLAecd
heavy chain = SEQ ID NO: 481

(M6903)
light chain = SEQ ID NO: 141

anti-TIM3-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 486

(M6903)
light chain = SEQ ID NO: 487

anti-TIM3-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 486

(M6903)
light chain = SEQ ID NO: 483

anti-TIM3-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 486

(M6903)
light chain = SEQ ID NO: 484

anti-TIM3-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 486

(M6903)
light chain = SEQ ID NO: 485

anti-TIM3-PD1ecd
heavy chain = SEQ ID NO: 486

(M6903)
light chain = SEQ ID NO: 141

anti-TIM3-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 488

(M6903)
light chain = SEQ ID NO: 487

anti-TIM3-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 488

(M6903)
light chain = SEQ ID NO: 482

anti-TIM3-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 488

(M6903)
light chain = SEQ ID NO: 484

anti-TIM3-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 488

(M6903)
light chain = SEQ ID NO: 485

anti-TIM3-SIGLEC10ecd
heavy chain = SEQ ID NO: 488

(M6903)
light chain = SEQ ID NO: 141

anti-TIM3-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 489

(M6903)
light chain = SEQ ID NO: 487

anti-TIM3-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 489

(M6903)
light chain = SEQ ID NO: 482

anti-TIM3-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 489

(M6903)
light chain = SEQ ID NO: 483

anti-TIM3-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 489

(M6903)
light chain = SEQ ID NO: 485

anti-TIM3-SIRPaecd
heavy chain = SEQ ID NO: 489

(M6903)
light chain = SEQ ID NO: 141

anti-TIM3-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 490

(M6903)
light chain = SEQ ID NO: 487

anti-TIM3-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 490

(M6903)
light chain = SEQ ID NO: 482

anti-TIM3-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 490

(M6903)
light chain = SEQ ID NO: 483

anti-TIM3-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 490

(M6903)
light chain = SEQ ID NO: 484

anti-TIM3-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 490

(M6903)
light chain = SEQ ID NO: 485

anti-TIM3-TGFbRecd
heavy chain = SEQ ID NO: 490

(M6903)
light chain = SEQ ID NO: 141

anti-TIM3-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 491

(M6903)
light chain = SEQ ID NO: 487

anti-TIM3-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 491

(M6903)
light chain = SEQ ID NO: 482

anti-TIM3-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 491

(M6903)
light chain = SEQ ID NO: 483

anti-TIM3-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 491

(M6903)
light chain = SEQ ID NO: 484

anti-TIM3-TIM3ecd
heavy chain = SEQ ID NO: 491

(M6903)
light chain = SEQ ID NO: 141

anti-TIM3-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 492

(M6903)
light chain = SEQ ID NO: 487

anti-TIM3-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 492

(M6903)
light chain = SEQ ID NO: 482

anti-TIM3-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 492

(M6903)
light chain = SEQ ID NO: 483

anti-TIM3-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 492

(M6903)
light chain = SEQ ID NO: 484

anti-TIM3-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 492

(M6903)
light chain = SEQ ID NO: 485

anti-TIM3-VEGFRecd
heavy chain = SEQ ID NO: 492

(M6903)
light chain = SEQ ID NO: 141

anti-41BB-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 493

(urelumab)
light chain = SEQ ID NO: 494

anti-41BB-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 493

(urelumab)
light chain = SEQ ID NO: 495

anti-41BB-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 493

(urelumab)
light chain = SEQ ID NO: 496

anti-41BB-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 493

(urelumab)
light chain = SEQ ID NO: 497

anti-41BB-BTLAecd
heavy chain = SEQ ID NO: 493

(urelumab)
light chain = SEQ ID NO: 2

anti-41BB-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 498

(urelumab)
light chain = SEQ ID NO: 499

anti-41BB-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 498

(urelumab)
light chain = SEQ ID NO: 495

anti-41BB-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 498

(urelumab)
light chain = SEQ ID NO: 496

anti-41BB-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 498

(urelumab)
light chain = SEQ ID NO: 497

anti-41BB-PD1ecd
heavy chain = SEQ ID NO: 498

(urelumab)
light chain = SEQ ID NO: 2

anti-41BB-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 500

(urelumab)
light chain = SEQ ID NO: 499

anti-41BB-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 500

(urelumab)
light chain = SEQ ID NO: 494

anti-41BB-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 500

(urelumab)
light chain = SEQ ID NO: 496

anti-41BB-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 500

(urelumab)
light chain = SEQ ID NO: 497

anti-41BB-SIGLEC10ecd
heavy chain = SEQ ID NO: 500

(urelumab)
light chain = SEQ ID NO: 2

anti-41BB-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 501

(urelumab)
light chain = SEQ ID NO: 499

anti-41BB-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 501

(urelumab)
light chain = SEQ ID NO: 494

anti-41BB-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 501

(urelumab)
light chain = SEQ ID NO: 495

anti-41BB-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 501

(urelumab)
light chain = SEQ ID NO: 497

anti-41BB-SIRPaecd
heavy chain = SEQ ID NO: 501

(urelumab)
light chain = SEQ ID NO: 2

anti-41BB-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 502

(urelumab)
light chain = SEQ ID NO: 499

anti-41BB-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 502

(urelumab)
light chain = SEQ ID NO: 494

anti-41BB-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 502

(urelumab)
light chain = SEQ ID NO: 495

anti-41BB-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 502

(urelumab)
light chain = SEQ ID NO: 496

anti-41BB-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 502

(urelumab)
light chain = SEQ ID NO: 497

anti-41BB-TGFbRecd
heavy chain = SEQ ID NO: 502

(urelumab)
light chain = SEQ ID NO: 2

anti-41BB-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 503

(urelumab)
light chain = SEQ ID NO: 499

anti-41BB-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 503

(urelumab)
light chain = SEQ ID NO: 494

anti-41BB-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 503

(urelumab)
light chain = SEQ ID NO: 495

anti-41BB-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 503

(urelumab)
light chain = SEQ ID NO: 496

anti-41BB-TIM3ecd
heavy chain = SEQ ID NO: 503

(urelumab)
light chain = SEQ ID NO: 2

anti-41BB-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 504

(urelumab)
light chain = SEQ ID NO: 499

anti-41BB-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 504

(urelumab)
light chain = SEQ ID NO: 494

anti-41BB-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 504

(urelumab)
light chain = SEQ ID NO: 495

anti-41BB-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 504

(urelumab)
light chain = SEQ ID NO: 496

anti-41BB-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 504

(urelumab)
light chain = SEQ ID NO: 497

anti-41BB-VEGFRecd
heavy chain = SEQ ID NO: 504

(urelumab)
light chain = SEQ ID NO: 2

anti-OX40-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 505

(GSK3174998)
light chain = SEQ ID NO: 506

anti-OX40-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 505

(GSK3174998)
light chain = SEQ ID NO: 507

anti-OX40-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 505

(GSK3174998)
light chain = SEQ ID NO: 508

anti-OX40-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 505

(GSK3174998)
light chain = SEQ ID NO: 509

anti-OX40-BTLAecd
heavy chain = SEQ ID NO: 505

(GSK3174998)
light chain = SEQ ID NO: 97

anti-OX40-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 510

(GSK3174998)
light chain = SEQ ID NO: 511

anti-OX40-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 510

(GSK3174998)
light chain = SEQ ID NO: 507

anti-OX40-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 510

(GSK3174998)
light chain = SEQ ID NO: 508

anti-OX40-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 510

(GSK3174998)
light chain = SEQ ID NO: 509

anti-OX40-PD1ecd
heavy chain = SEQ ID NO: 510

(GSK3174998)
light chain = SEQ ID NO: 97

anti-OX40-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 512

(GSK3174998)
light chain = SEQ ID NO: 511

anti-OX40-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 512

(GSK3174998)
light chain = SEQ ID NO: 506

anti-OX40-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 512

(GSK3174998)
light chain = SEQ ID NO: 508

anti-OX40-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 512

(GSK3174998)
light chain = SEQ ID NO: 509

anti-OX40-SIGLEC10ecd
heavy chain = SEQ ID NO: 512

(GSK3174998)
light chain = SEQ ID NO: 97

anti-OX40-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 513

(GSK3174998)
light chain = SEQ ID NO: 511

anti-OX40-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 513

(GSK3174998)
light chain = SEQ ID NO: 506

anti-OX40-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 513

(GSK3174998)
light chain = SEQ ID NO: 507

anti-OX40-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 513

(GSK3174998)
light chain = SEQ ID NO: 509

anti-OX40-SIRPaecd
heavy chain = SEQ ID NO: 513

(GSK3174998)
light chain = SEQ ID NO: 97

anti-OX40-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 514

(GSK3174998)
light chain = SEQ ID NO: 511

anti-OX40-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 514

(GSK3174998)
light chain = SEQ ID NO: 506

anti-OX40-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 514

(GSK3174998)
light chain = SEQ ID NO: 507

anti-OX40-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 514

(GSK3174998)
light chain = SEQ ID NO: 508

anti-OX40-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 514

(GSK3174998)
light chain = SEQ ID NO: 509

anti-OX40-TGFbRecd
heavy chain = SEQ ID NO: 514

(GSK3174998)
light chain = SEQ ID NO: 97

anti-OX40-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 515

(GSK3174998)
light chain = SEQ ID NO: 511

anti-OX40-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 515

(GSK3174998)
light chain = SEQ ID NO: 506

anti-OX40-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 515

(GSK3174998)
light chain = SEQ ID NO: 507

anti-OX40-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 515

(GSK3174998)
light chain = SEQ ID NO: 508

anti-OX40-TIM3ecd
heavy chain = SEQ ID NO: 515

(GSK3174998)
light chain = SEQ ID NO: 97

anti-OX40-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 516

(GSK3174998)
light chain = SEQ ID NO: 511

anti-OX40-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 516

(GSK3174998)
light chain = SEQ ID NO: 506

anti-OX40-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 516

(GSK3174998)
light chain = SEQ ID NO: 507

anti-OX40-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 516

(GSK3174998)
light chain = SEQ ID NO: 508

anti-OX40-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 516

(GSK3174998)
light chain = SEQ ID NO: 509

anti-OX40-VEGFRecd
heavy chain = SEQ ID NO: 516

(GSK3174998)
light chain = SEQ ID NO: 97

anti-ICOS-BTLAecd-PD1ecd
heavy chain = SEQ ID NO: 517

(GSK3359609)
light chain = SEQ ID NO: 518

anti-ICOS-BTLAecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 517

(GSK3359609)
light chain = SEQ ID NO: 519

anti-ICOS-BTLAecd-SIRPaecd
heavy chain = SEQ ID NO: 517

(GSK3359609)
light chain = SEQ ID NO: 520

anti-ICOS-BTLAecd-TIM3ecd
heavy chain = SEQ ID NO: 517

(GSK3359609)
light chain = SEQ ID NO: 521

anti-ICOS-BTLAecd
heavy chain = SEQ ID NO: 517

(GSK3359609)
light chain = SEQ ID NO: 59

anti-ICOS-PD1ecd-BTLAecd
heavy chain = SEQ ID NO: 522

(GSK3359609)
light chain = SEQ ID NO: 523

anti-ICOS-PD1ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 522

(GSK3359609)
light chain = SEQ ID NO: 519

anti-ICOS-PD1ecd-SIRPaecd
heavy chain = SEQ ID NO: 522

(GSK3359609)
light chain = SEQ ID NO: 520

anti-ICOS-PD1ecd-TIM3ecd
heavy chain = SEQ ID NO: 522

(GSK3359609)
light chain = SEQ ID NO: 521

anti-ICOS-PD1ecd
heavy chain = SEQ ID NO: 522

(GSK3359609)
light chain = SEQ ID NO: 59

anti-ICOS-SIGLEC10ecd-BTLAecd
heavy chain = SEQ ID NO: 524

(GSK3359609)
light chain = SEQ ID NO: 523

anti-ICOS-SIGLEC10ecd-PD1ecd
heavy chain = SEQ ID NO: 524

(GSK3359609)
light chain = SEQ ID NO: 518

anti-ICOS-SIGLEC10ecd-SIRPaecd
heavy chain = SEQ ID NO: 524

(GSK3359609)
light chain = SEQ ID NO: 520

anti-ICOS-SIGLEC10ecd-TIM3ecd
heavy chain = SEQ ID NO: 524

(GSK3359609)
light chain = SEQ ID NO: 521

anti-ICOS-SIGLEC10ecd
heavy chain = SEQ ID NO: 524

(GSK3359609)
light chain = SEQ ID NO: 59

anti-ICOS-SIRPaecd-BTLAecd
heavy chain = SEQ ID NO: 525

(GSK3359609)
light chain = SEQ ID NO: 523

anti-ICOS-SIRPaecd-PD1ecd
heavy chain = SEQ ID NO: 525

(GSK3359609)
light chain = SEQ ID NO: 518

anti-ICOS-SIRPaecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 525

(GSK3359609)
light chain = SEQ ID NO: 519

anti-ICOS-SIRPaecd-TIM3ecd
heavy chain = SEQ ID NO: 525

(GSK3359609)
light chain = SEQ ID NO: 521

anti-ICOS-SIRPaecd
heavy chain = SEQ ID NO: 525

(GSK3359609)
light chain = SEQ ID NO: 59

anti-ICOS-TGFbRecd-BTLAecd
heavy chain = SEQ ID NO: 526

(GSK3359609)
light chain = SEQ ID NO: 523

anti-ICOS-TGFbRecd-PD1ecd
heavy chain = SEQ ID NO: 526

(GSK3359609)
light chain = SEQ ID NO: 518

anti-ICOS-TGFbRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 526

(GSK3359609)
light chain = SEQ ID NO: 519

anti-ICOS-TGFbRecd-SIRPaecd
heavy chain = SEQ ID NO: 526

(GSK3359609)
light chain = SEQ ID NO: 520

anti-ICOS-TGFbRecd-TIM3ecd
heavy chain = SEQ ID NO: 526

(GSK3359609)
light chain = SEQ ID NO: 521

anti-ICOS-TGFbRecd
heavy chain = SEQ ID NO: 526

(GSK3359609)
light chain = SEQ ID NO: 59

anti-ICOS-TIM3ecd-BTLAecd
heavy chain = SEQ ID NO: 527

(GSK3359609)
light chain = SEQ ID NO: 523

anti-ICOS-TIM3ecd-PD1ecd
heavy chain = SEQ ID NO: 527

(GSK3359609)
light chain = SEQ ID NO: 518

anti-ICOS-TIM3ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 527

(GSK3359609)
light chain = SEQ ID NO: 519

anti-ICOS-TIM3ecd-SIRPaecd
heavy chain = SEQ ID NO: 527

(GSK3359609)
light chain = SEQ ID NO: 520

anti-ICOS-TIM3ecd
heavy chain = SEQ ID NO: 527

(GSK3359609)
light chain = SEQ ID NO: 59

anti-ICOS-VEGFRecd-BTLAecd
heavy chain = SEQ ID NO: 528

(GSK3359609)
light chain = SEQ ID NO: 523

anti-ICOS-VEGFRecd-PD1ecd
heavy chain = SEQ ID NO: 528

(GSK3359609)
light chain = SEQ ID NO: 518

anti-ICOS-VEGFRecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 528

(GSK3359609)
light chain = SEQ ID NO: 519

anti-ICOS-VEGFRecd-SIRPaecd
heavy chain = SEQ ID NO: 528

(GSK3359609)
light chain = SEQ ID NO: 520

anti-ICOS-VEGFRecd-TIM3ecd
heavy chain = SEQ ID NO: 528

(GSK3359609)
light chain = SEQ ID NO: 521

anti-ICOS-VEGFRecd
heavy chain = SEQ ID NO: 528

(GSK3359609)
light chain = SEQ ID NO: 59

BTLAecd-Fc-PD1ecd
SEQ ID NO: 529

BTLAecd-Fc-SIGLEC10ecd
SEQ ID NO: 530

BTLAecd-Fc-SIRPaecd
SEQ ID NO: 531

BTLAecd-Fc-TGFbRecd
SEQ ID NO: 532

BTLAecd-Fc-TIM3ecd
SEQ ID NO: 533

BTLAecd-Fc-VEGFRecd
SEQ ID NO: 534

PD1ecd-Fc-BTLAecd
SEQ ID NO: 535

PD1ecd-Fc-SIGLEC10ecd
SEQ ID NO: 536

PD1ecd-Fc-SIRPaecd
SEQ ID NO: 537

PD1ecd-Fc-TGFbRecd
SEQ ID NO: 538

PD1ecd-Fc-TIM3ecd
SEQ ID NO: 539

PD1ecd-Fc-VEGFRecd
SEQ ID NO: 540

SIGLEC10ecd-Fc-BTLAecd
SEQ ID NO: 541

SIGLEC10ecd-Fc-PD1ecd
SEQ ID NO: 542

SIGLEC10ecd-Fc-SIRPaecd
SEQ ID NO: 543

SIGLEC10ecd-Fc-TGFbRecd
SEQ ID NO: 544

SIGLEC10ecd-Fc-TIM3ecd
SEQ ID NO: 545

SIGLEC10ecd-Fc-VEGFRecd
SEQ ID NO: 546

SIRPaecd-Fc-BTLAecd
SEQ ID NO: 547

SIRPaecd-Fc-PD1ecd
SEQ ID NO: 548

SIRPaecd-Fc-SIGLEC10ecd
SEQ ID NO: 549

SIRPaecd-Fc-TGFbRecd
SEQ ID NO: 550

SIRPaecd-Fc-TIM3ecd
SEQ ID NO: 551

SIRPaecd-Fc-VEGFRecd
SEQ ID NO: 552

TGFbRecd-Fc-BTLAecd
SEQ ID NO: 553

TGFbRecd-Fc-PD1ecd
SEQ ID NO: 554

TGFbRecd-Fc-SIGLEC10ecd
SEQ ID NO: 555

TGFbRecd-Fc-SIRPaecd
SEQ ID NO: 556

TGFbRecd-Fc-TIM3ecd
SEQ ID NO: 557

TGFbRecd-Fc-VEGFRecd
SEQ ID NO: 558

TIM3ecd-Fc-BTLAecd
SEQ ID NO: 559

TIM3ecd-Fc-PD1ecd
SEQ ID NO: 560

TIM3ecd-Fc-SIGLEC10ecd
SEQ ID NO: 561

TIM3ecd-Fc-SIRPaecd
SEQ ID NO: 562

TIM3ecd-Fc-TGFbRecd
SEQ ID NO: 563

TIM3ecd-Fc-VEGFRecd
SEQ ID NO: 564

VEGFRecd-Fc-BTLAecd
SEQ ID NO: 565

VEGFRecd-Fc-PD1ecd
SEQ ID NO: 566

VEGFRecd-Fc-SIGLEC10ecd
SEQ ID NO: 567

VEGFRecd-Fc-SIRPaecd
SEQ ID NO: 568

VEGFRecd-Fc-TGFbRecd
SEQ ID NO: 569

VEGFRecd-Fc-TIM3ecd
SEQ ID NO: 570

BTLAecd-Fc-IL12ecd
SEQ ID NO: 571

IL12ecd-Fc-BTLAecd
SEQ ID NO: 572

BTLAecd-Fc-IL15ecd
SEQ ID NO: 573

IL15ecd-Fc-BTLAecd
SEQ ID NO: 574

PD1ecd-Fc-IL12ecd
SEQ ID NO: 575

IL12ecd-Fc-PD1ecd
SEQ ID NO: 576

PD1ecd-Fc-IL15ecd
SEQ ID NO: 577

IL15ecd-Fc-PD1ecd
SEQ ID NO: 578

SIGLEC10ecd-Fc-IL12ecd
SEQ ID NO: 579

IL12ecd-Fc-SIGLEC10ecd
SEQ ID NO: 580

SIGLEC10ecd-Fc-IL15ecd
SEQ ID NO: 581

IL15ecd-Fc-SIGLEC10ecd
SEQ ID NO: 582

SIRPaecd-Fc-IL12ecd
SEQ ID NO: 583

IL12ecd-Fc-SIRPaecd
SEQ ID NO: 584

SIRPaecd-Fc-IL15ecd
SEQ ID NO: 585

IL15ecd-Fc-SIRPaecd
SEQ ID NO: 586

TGFbRecd-Fc-IL12ecd
SEQ ID NO: 587

IL12ecd-Fc-TGFbRecd
SEQ ID NO: 588

TGFbRecd-Fc-IL15ecd
SEQ ID NO: 589

IL15ecd-Fc-TGFbRecd
SEQ ID NO: 590

TIM3ecd-Fc-IL12ecd
SEQ ID NO: 591

IL12ecd-Fc-TIM3ecd
SEQ ID NO: 592

TIM3ecd-Fc-IL15ecd
SEQ ID NO: 593

IL15ecd-Fc-TIM3ecd
SEQ ID NO: 594

VEGFRecd-Fc-IL12ecd
SEQ ID NO: 595

IL12ecd-Fc-VEGFRecd
SEQ ID NO: 596

VEGFRecd-Fc-IL15ecd
SEQ ID NO: 597

IL15ecd-Fc-VEGFRecd
SEQ ID NO: 598

SIGLEC10ecd-Fc-41BBLecd
SEQ ID NO: 599

41BBLecd-Fc-SIGLEC10ecd
SEQ ID NO: 600

SIGLEC10ecd-Fc-CD30Lecd
SEQ ID NO: 601

CD30Lecd-Fc-SIGLEC10ecd
SEQ ID NO: 602

SIGLEC10ecd-Fc-CD40Lecd
SEQ ID NO: 603

CD40Lecd-Fc-SIGLEC10ecd
SEQ ID NO: 604

SIGLEC10ecd-Fc-CD70ecd
SEQ ID NO: 605

CD70ecd-Fc-SIGLEC10ecd
SEQ ID NO: 606

SIGLEC10ecd-Fc-GITRLecd
SEQ ID NO: 607

GITRLecd-Fc-SIGLEC10ecd
SEQ ID NO: 608

SIGLEC10ecd-Fc-ICOSLecd
SEQ ID NO: 609

ICOSLecd-Fc-SIGLEC10ecd
SEQ ID NO: 610

SIGLEC10ecd-Fc-IL12ecd
SEQ ID NO: 579

IL12ecd-Fc-SIGLEC10ecd
SEQ ID NO: 580

SIGLEC10ecd-Fc-IL15ecd
SEQ ID NO: 581

IL15ecd-Fc-SIGLEC10ecd
SEQ ID NO: 582

SIGLEC10ecd-Fc-LIGHTecd
SEQ ID NO: 611

LIGHTecd-Fc-SIGLEC10ecd
SEQ ID NO: 612

SIGLEC10ecd-Fc-OX40Lecd
SEQ ID NO: 613

OX40Lecd-Fc-SIGLEC10ecd
SEQ ID NO: 614

TGFbRecd-Fc-41BBLecd
SEQ ID NO: 615

41BBLecd-Fc-TGFbRecd
SEQ ID NO: 616

TGFbRecd-Fc-CD30Lecd
SEQ ID NO: 617

CD30Lecd-Fc-TGFbRecd
SEQ ID NO: 618

TGFbRecd-Fc-CD40Lecd
SEQ ID NO: 619

CD40Lecd-Fc-TGFbRecd
SEQ ID NO: 620

TGFbRecd-Fc-CD70ecd
SEQ ID NO: 621

CD70ecd-Fc-TGFbRecd
SEQ ID NO: 622

TGFbRecd-Fc-GITRLecd
SEQ ID NO: 623

GITRLecd-Fc-TGFbRecd
SEQ ID NO: 624

TGFbRecd-Fc-ICOSLecd
SEQ ID NO: 625

ICOSLecd-Fc-TGFbRecd
SEQ ID NO: 626

TGFbRecd-Fc-IL12ecd
SEQ ID NO: 587

IL12ecd-Fc-TGFbRecd
SEQ ID NO: 588

TGFbRecd-Fc-IL15ecd
SEQ ID NO: 589

IL15ecd-Fc-TGFbRecd
SEQ ID NO: 590

TGFbRecd-Fc-LIGHTecd
SEQ ID NO: 627

LIGHTecd-Fc-TGFbRecd
SEQ ID NO: 628

TGFbRecd-Fc-OX40Lecd
SEQ ID NO: 629

OX40Lecd-Fc-TGFbRecd
SEQ ID NO: 630

VEGFRecd-Fc-41BBLecd
SEQ ID NO: 631

41BBLecd-Fc-VEGFRecd
SEQ ID NO: 632

VEGFRecd-Fc-CD30Lecd
SEQ ID NO: 633

CD30Lecd-Fc-VEGFRecd
SEQ ID NO: 634

VEGFRecd-Fc-CD40Lecd
SEQ ID NO: 635

CD40Lecd-Fc-VEGFRecd
SEQ ID NO: 636

VEGFRecd-Fc-CD70ecd
SEQ ID NO: 637

CD70ecd-Fc-VEGFRecd
SEQ ID NO: 638

VEGFRecd-Fc-GITRLecd
SEQ ID NO: 639

GITRLecd-Fc-VEGFRecd
SEQ ID NO: 640

VEGFRecd-Fc-ICOSLecd
SEQ ID NO: 641

ICOSLecd-Fc-VEGFRecd
SEQ ID NO: 642

VEGFRecd-Fc-IL12ecd
SEQ ID NO: 595

IL12ecd-Fc-VEGFRecd
SEQ ID NO: 596

VEGFRecd-Fc-IL15ecd
SEQ ID NO: 597

IL15ecd-Fc-VEGFRecd
SEQ ID NO: 598

VEGFRecd-Fc-LIGHTecd
SEQ ID NO: 643

LIGHTecd-Fc-VEGFRecd
SEQ ID NO: 644

VEGFRecd-Fc-OX40Lecd
SEQ ID NO: 645

OX40Lecd-Fc-VEGFRecd
SEQ ID NO: 646

anti-PDL1-41BBLecd
heavy chain = SEQ ID NO: 647

(atezolizumab)
light chain = SEQ ID NO: 109

anti-PDL1-41BBLecd-BTLAecd
heavy chain = SEQ ID NO: 647

(atezolizumab)
light chain = SEQ ID NO: 464

anti-PDL1-41BBLecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 647

(atezolizumab)
light chain = SEQ ID NO: 460

anti-PDL1-41BBLecd-SIRPaecd
heavy chain = SEQ ID NO: 647

(atezolizumab)
light chain = SEQ ID NO: 461

anti-PDL1-41BBLecd-TIM3ecd
heavy chain = SEQ ID NO: 647

(atezolizumab)
light chain = SEQ ID NO: 462

anti-PDL1-CD30Lecd
heavy chain = SEQ ID NO: 648

(atezolizumab)
light chain = SEQ ID NO: 109

anti-PDL1-CD30Lecd-BTLAecd
heavy chain = SEQ ID NO: 648

(atezolizumab)
light chain = SEQ ID NO: 464

anti-PDL1-CD30Lecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 648

(atezolizumab)
light chain = SEQ ID NO: 460

anti-PDL1-CD30Lecd-SIRPaecd
heavy chain = SEQ ID NO: 648

(atezolizumab)
light chain = SEQ ID NO: 461

anti-PDL1-CD30Lecd-TIM3ecd
heavy chain = SEQ ID NO: 648

(atezolizumab)
light chain = SEQ ID NO: 462

anti-PDL1-CD40Lecd
heavy chain = SEQ ID NO: 649

(atezolizumab)
light chain = SEQ ID NO: 109

anti-PDL1-CD40Lecd-BTLAecd
heavy chain = SEQ ID NO: 649

(atezolizumab)
light chain = SEQ ID NO: 464

anti-PDL1-CD40Lecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 649

(atezolizumab)
light chain = SEQ ID NO: 460

anti-PDL1-CD40Lecd-SIRPaecd
heavy chain = SEQ ID NO: 649

(atezolizumab)
light chain = SEQ ID NO: 461

anti-PDL1-CD40Lecd-TIM3ecd
heavy chain = SEQ ID NO: 649

(atezolizumab)
light chain = SEQ ID NO: 462

anti-PDL1-CD70ecd
heavy chain = SEQ ID NO: 650

(atezolizumab)
light chain = SEQ ID NO: 109

anti-PDL1-CD70ecd-BTLAecd
heavy chain = SEQ ID NO: 650

(atezolizumab)
light chain = SEQ ID NO: 464

anti-PDL1-CD70ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 650

(atezolizumab)
light chain = SEQ ID NO: 460

anti-PDL1-CD70ecd-SIRPaecd
heavy chain = SEQ ID NO: 650

(atezolizumab)
light chain = SEQ ID NO: 461

anti-PDL1-CD70ecd-TIM3ecd
heavy chain = SEQ ID NO: 650

(atezolizumab)
light chain = SEQ ID NO: 462

anti-PDL1-GITRLecd
heavy chain = SEQ ID NO: 651

(atezolizumab)
light chain = SEQ ID NO: 109

anti-PDL1-GITRLecd-BTLAecd
heavy chain = SEQ ID NO: 651

(atezolizumab)
light chain = SEQ ID NO: 464

anti-PDL1-GITRLecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 651

(atezolizumab)
light chain = SEQ ID NO: 460

anti-PDL1-GITRLecd-SIRPaecd
heavy chain = SEQ ID NO: 651

(atezolizumab)
light chain = SEQ ID NO: 461

anti-PDL1-GITRLecd-TIM3ecd
heavy chain = SEQ ID NO: 651

(atezolizumab)
light chain = SEQ ID NO: 462

anti-PDL1-ICOSLecd
heavy chain = SEQ ID NO: 652

(atezolizumab)
light chain = SEQ ID NO: 109

anti-PDL1-ICOSLecd-BTLAecd
heavy chain = SEQ ID NO: 652

(atezolizumab)
light chain = SEQ ID NO: 464

anti-PDL1-ICOSLecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 652

(atezolizumab)
light chain = SEQ ID NO: 460

anti-PDL1-ICOSLecd-SIRPaecd
heavy chain = SEQ ID NO: 652

(atezolizumab)
light chain = SEQ ID NO: 461

anti-PDL1-ICOSLecd-TIM3ecd
heavy chain = SEQ ID NO: 652

(atezolizumab)
light chain = SEQ ID NO: 462

anti-PDL1-IL12ecd
heavy chain = SEQ ID NO: 653

(atezolizumab)
light chain = SEQ ID NO: 109

anti-PDL1-IL12ecd-BTLAecd
heavy chain = SEQ ID NO: 653

(atezolizumab)
light chain = SEQ ID NO: 464

anti-PDL1-IL12ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 653

(atezolizumab)
light chain = SEQ ID NO: 460

anti-PDL1-IL12ecd-SIRPaecd
heavy chain = SEQ ID NO: 653

(atezolizumab)
light chain = SEQ ID NO: 461

anti-PDL1-IL12ecd-TIM3ecd
heavy chain = SEQ ID NO: 653

(atezolizumab)
light chain = SEQ ID NO: 462

anti-PDL1-IL15ecd
heavy chain = SEQ ID NO: 654

(atezolizumab)
light chain = SEQ ID NO: 109

anti-PDL1-IL15ecd-BTLAecd
heavy chain = SEQ ID NO: 654

(atezolizumab)
light chain = SEQ ID NO: 464

anti-PDL1-IL15ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 654

(atezolizumab)
light chain = SEQ ID NO: 460

anti-PDL1-IL15ecd-SIRPaecd
heavy chain = SEQ ID NO: 654

(atezolizumab)
light chain = SEQ ID NO: 461

anti-PDL1-IL15ecd-TIM3ecd
heavy chain = SEQ ID NO: 654

(atezolizumab)
light chain = SEQ ID NO: 462

anti-PDL1-LIGHTecd
heavy chain = SEQ ID NO: 655

(atezolizumab)
light chain = SEQ ID NO: 109

anti-PDL1-LIGHTecd-BTLAecd
heavy chain = SEQ ID NO: 655

(atezolizumab)
light chain = SEQ ID NO: 464

anti-PDL1-LIGHTecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 655

(atezolizumab)
light chain = SEQ ID NO: 460

anti-PDL1-LIGHTecd-SIRPaecd
heavy chain = SEQ ID NO: 655

(atezolizumab)
light chain = SEQ ID NO: 461

anti-PDL1-LIGHTecd-TIM3ecd
heavy chain = SEQ ID NO: 655

(atezolizumab)
light chain = SEQ ID NO: 462

anti-PDL1-OX40Lecd
heavy chain = SEQ ID NO: 656

(atezolizumab)
light chain = SEQ ID NO: 109

anti-PDL1-OX40Lecd-BTLAecd
heavy chain = SEQ ID NO: 656

(atezolizumab)
light chain = SEQ ID NO: 464

anti-PDL1-OX40Lecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 656

(atezolizumab)
light chain = SEQ ID NO: 460

anti-PDL1-OX40Lecd-SIRPaecd
heavy chain = SEQ ID NO: 656

(atezolizumab)
light chain = SEQ ID NO: 461

anti-PDL1-OX40Lecd-TIM3ecd
heavy chain = SEQ ID NO: 656

(atezolizumab)
light chain = SEQ ID NO: 462

anti-PDL1-BTLAecd-41BBLecd
heavy chain = SEQ ID NO: 459

(atezolizumab)
light chain = SEQ ID NO: 657

anti-PDL1-BTLAecd-CD30Lecd
heavy chain = SEQ ID NO: 459

(atezolizumab)
light chain = SEQ ID NO: 658

anti-PDL1-BTLAecd-CD40Lecd
heavy chain = SEQ ID NO: 459

(atezolizumab)
light chain = SEQ ID NO: 659

anti-PDL1-BTLAecd-CD70ecd
heavy chain = SEQ ID NO: 459

(atezolizumab)
light chain = SEQ ID NO: 660

anti-PDL1-BTLAecd-GITRLecd
heavy chain = SEQ ID NO: 459

(atezolizumab)
light chain = SEQ ID NO: 661

anti-PDL1-BTLAecd-ICOSLecd
heavy chain = SEQ ID NO: 459

(atezolizumab)
light chain = SEQ ID NO: 662

anti-PDL1-BTLAecd-IL12ecd
heavy chain = SEQ ID NO: 459

(atezolizumab)
light chain = SEQ ID NO: 663

anti-PDL1-BTLAecd-IL15ecd
heavy chain = SEQ ID NO: 459

(atezolizumab)
light chain = SEQ ID NO: 664

anti-PDL1-BTLAecd-LIGHTecd
heavy chain = SEQ ID NO: 459

(atezolizumab)
light chain = SEQ ID NO: 665

anti-PDL1-BTLAecd-OX40Lecd
heavy chain = SEQ ID NO: 459

(atezolizumab)
light chain = SEQ ID NO: 666

anti-PDL1-SIGLEC10ecd-41BBLecd
heavy chain = SEQ ID NO: 463

(atezolizumab)
light chain = SEQ ID NO: 657

anti-PDL1-SIGLEC10ecd-CD30Lecd
heavy chain = SEQ ID NO: 463

(atezolizumab)
light chain = SEQ ID NO: 658

anti-PDL1-SIGLEC10ecd-CD40Lecd
heavy chain = SEQ ID NO: 463

(atezolizumab)
light chain = SEQ ID NO: 659

anti-PDL1-SIGLEC10ecd-CD70ecd
heavy chain = SEQ ID NO: 463

(atezolizumab)
light chain = SEQ ID NO: 660

anti-PDL1-SIGLEC10ecd-GITRLecd
heavy chain = SEQ ID NO: 463

(atezolizumab)
light chain = SEQ ID NO: 661

anti-PDL1-SIGLEC10ecd-ICOSLecd
heavy chain = SEQ ID NO: 463

(atezolizumab)
light chain = SEQ ID NO: 662

anti-PDL1-SIGLEC10ecd-IL12ecd
heavy chain = SEQ ID NO: 463

(atezolizumab)
light chain = SEQ ID NO: 663

anti-PDL1-SIGLEC10ecd-IL15ecd
heavy chain = SEQ ID NO: 463

(atezolizumab)
light chain = SEQ ID NO: 664

anti-PDL1-SIGLEC10ecd-LIGHTecd
heavy chain = SEQ ID NO: 463

(atezolizumab)
light chain = SEQ ID NO: 665

anti-PDL1-SIGLEC10ecd-OX40Lecd
heavy chain = SEQ ID NO: 463

(atezolizumab)
light chain = SEQ ID NO: 666

anti-PDL1-SIRPaecd-41BBLecd
heavy chain = SEQ ID NO: 465

(atezolizumab)
light chain = SEQ ID NO: 657

anti-PDL1-SIRPaecd-CD30Lecd
heavy chain = SEQ ID NO: 465

(atezolizumab)
light chain = SEQ ID NO: 658

anti-PDL1-SIRPaecd-CD40Lecd
heavy chain = SEQ ID NO: 465

(atezolizumab)
light chain = SEQ ID NO: 659

anti-PDL1-SIRPaecd-CD70ecd
heavy chain = SEQ ID NO: 465

(atezolizumab)
light chain = SEQ ID NO: 660

anti-PDL1-SIRPaecd-GITRLecd
heavy chain = SEQ ID NO: 465

(atezolizumab)
light chain = SEQ ID NO: 661

anti-PDL1-SIRPaecd-ICOSLecd
heavy chain = SEQ ID NO: 465

(atezolizumab)
light chain = SEQ ID NO: 662

anti-PDL1-SIRPaecd-IL12ecd
heavy chain = SEQ ID NO: 465

(atezolizumab)
light chain = SEQ ID NO: 663

anti-PDL1-SIRPaecd-IL15ecd
heavy chain = SEQ ID NO: 465

(atezolizumab)
light chain = SEQ ID NO: 664

anti-PDL1-SIRPaecd-LIGHTecd
heavy chain = SEQ ID NO: 465

(atezolizumab)
light chain = SEQ ID NO: 665

anti-PDL1-SIRPaecd-OX40Lecd
heavy chain = SEQ ID NO: 465

(atezolizumab)
light chain = SEQ ID NO: 666

anti-PDL1-TGFbRecd-41BBLecd
heavy chain = SEQ ID NO: 466

(atezolizumab)
light chain = SEQ ID NO: 657

anti-PDL1-TGFbRecd-CD30Lecd
heavy chain = SEQ ID NO: 466

(atezolizumab)
light chain = SEQ ID NO: 658

anti-PDL1-TGFbRecd-CD40Lecd
heavy chain = SEQ ID NO: 466

(atezolizumab)
light chain = SEQ ID NO: 659

anti-PDL1-TGFbRecd-CD70ecd
heavy chain = SEQ ID NO: 466

(atezolizumab)
light chain = SEQ ID NO: 660

anti-PDL1-TGFbRecd-GITRLecd
heavy chain = SEQ ID NO: 466

(atezolizumab)
light chain = SEQ ID NO: 661

anti-PDL1-TGFbRecd-ICOSLecd
heavy chain = SEQ ID NO: 466

(atezolizumab)
light chain = SEQ ID NO: 662

anti-PDL1-TGFbRecd-IL12ecd
heavy chain = SEQ ID NO: 466

(atezolizumab)
light chain = SEQ ID NO: 663

anti-PDL1-TGFbRecd-IL15ecd
heavy chain = SEQ ID NO: 466

(atezolizumab)
light chain = SEQ ID NO: 664

anti-PDL1-TGFbRecd-LIGHTecd
heavy chain = SEQ ID NO: 466

(atezolizumab)
light chain = SEQ ID NO: 665

anti-PDL1-TGFbRecd-OX40Lecd
heavy chain = SEQ ID NO: 466

(atezolizumab)
light chain = SEQ ID NO: 666

anti-PDL1-TIM3ecd-41BBLecd
heavy chain = SEQ ID NO: 467

(atezolizumab)
light chain = SEQ ID NO: 657

anti-PDL1-TIM3ecd-CD30Lecd
heavy chain = SEQ ID NO: 467

(atezolizumab)
light chain = SEQ ID NO: 658

anti-PDL1-TIM3ecd-CD40Lecd
heavy chain = SEQ ID NO: 467

(atezolizumab)
light chain = SEQ ID NO: 659

anti-PDL1-TIM3ecd-CD70ecd
heavy chain = SEQ ID NO: 467

(atezolizumab)
light chain = SEQ ID NO: 660

anti-PDL1-TIM3ecd-GITRLecd
heavy chain = SEQ ID NO: 467

(atezolizumab)
light chain = SEQ ID NO: 661

anti-PDL1-TIM3ecd-ICOSLecd
heavy chain = SEQ ID NO: 467

(atezolizumab)
light chain = SEQ ID NO: 662

anti-PDL1-TIM3ecd-IL12ecd
heavy chain = SEQ ID NO: 467

(atezolizumab)
light chain = SEQ ID NO: 663

anti-PDL1-TIM3ecd-IL15ecd
heavy chain = SEQ ID NO: 467

(atezolizumab)
light chain = SEQ ID NO: 664

anti-PDL1-TIM3ecd-LIGHTecd
heavy chain = SEQ ID NO: 467

(atezolizumab)
light chain = SEQ ID NO: 665

anti-PDL1-TIM3ecd-OX40Lecd
heavy chain = SEQ ID NO: 467

(atezolizumab)
light chain = SEQ ID NO: 666

anti-PDL1-VEGFRecd-41BBLecd
heavy chain = SEQ ID NO: 468

(atezolizumab)
light chain = SEQ ID NO: 657

anti-PDL1-VEGFRecd-CD30Lecd
heavy chain = SEQ ID NO: 468

(atezolizumab)
light chain = SEQ ID NO: 658

anti-PDL1-VEGFRecd-CD40Lecd
heavy chain = SEQ ID NO: 468

(atezolizumab)
light chain = SEQ ID NO: 659

anti-PDL1-VEGFRecd-CD70ecd
heavy chain = SEQ ID NO: 468

(atezolizumab)
light chain = SEQ ID NO: 660

anti-PDL1-VEGFRecd-GITRLecd
heavy chain = SEQ ID NO: 468

(atezolizumab)
light chain = SEQ ID NO: 661

anti-PDL1-VEGFRecd-ICOSLecd
heavy chain = SEQ ID NO: 468

(atezolizumab)
light chain = SEQ ID NO: 662

anti-PDL1-VEGFRecd-IL12ecd
heavy chain = SEQ ID NO: 468

(atezolizumab)
light chain = SEQ ID NO: 663

anti-PDL1-VEGFRecd-IL15ecd
heavy chain = SEQ ID NO: 468

(atezolizumab)
light chain = SEQ ID NO: 664

anti-PDL1-VEGFRecd-LIGHTecd
heavy chain = SEQ ID NO: 468

(atezolizumab)
light chain = SEQ ID NO: 665

anti-PDL1-VEGFRecd-OX40Lecd
heavy chain = SEQ ID NO: 468

(atezolizumab)
light chain = SEQ ID NO: 666

anti-EGFR-41BBLecd
heavy chain = SEQ ID NO: 667

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFR-41BBLecd-BTLAecd
heavy chain = SEQ ID NO: 667

(cetuximab)
light chain = SEQ ID NO: 226

anti-EGFR-41BBLecd-PD1ecd
heavy chain = SEQ ID NO: 667

(cetuximab)
light chain = SEQ ID NO: 221

anti-EGFR-41BBLecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 667

(cetuximab)
light chain = SEQ ID NO: 222

anti-EGFR-41BBLecd-SIRPaecd
heavy chain = SEQ ID NO: 667

(cetuximab)
light chain = SEQ ID NO: 223

anti-EGFR-41BBLecd-TIM3ecd
heavy chain = SEQ ID NO: 667

(cetuximab)
light chain = SEQ ID NO: 224

anti-EGFR-CD30Lecd
heavy chain = SEQ ID NO: 668

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFR-CD30Lecd-BTLAecd
heavy chain = SEQ ID NO: 668

(cetuximab)
light chain = SEQ ID NO: 226

anti-EGFR-CD30Lecd-PD1ecd
heavy chain = SEQ ID NO: 668

(cetuximab)
light chain = SEQ ID NO: 221

anti-EGFR-CD30Lecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 668

(cetuximab)
light chain = SEQ ID NO: 222

anti-EGFR-CD30Lecd-SIRPaecd
heavy chain = SEQ ID NO: 668

(cetuximab)
light chain = SEQ ID NO: 223

anti-EGFR-CD30Lecd-TIM3ecd
heavy chain = SEQ ID NO: 668

(cetuximab)
light chain = SEQ ID NO: 224

anti-EGFR-CD40Lecd
heavy chain = SEQ ID NO: 669

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFR-CD40Lecd-BTLAecd
heavy chain = SEQ ID NO: 669

(cetuximab)
light chain = SEQ ID NO: 226

anti-EGFR-CD40Lecd-PD1ecd
heavy chain = SEQ ID NO: 669

(cetuximab)
light chain = SEQ ID NO: 221

anti-EGFR-CD40Lecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 669

(cetuximab)
light chain = SEQ ID NO: 222

anti-EGFR-CD40Lecd-SIRPaecd
heavy chain = SEQ ID NO: 669

(cetuximab)
light chain = SEQ ID NO: 223

anti-EGFR-CD40Lecd-TIM3ecd
heavy chain = SEQ ID NO: 669

(cetuximab)
light chain = SEQ ID NO: 224

anti-EGFR-CD70ecd
heavy chain = SEQ ID NO: 670

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFR-CD70ecd-BTLAecd
heavy chain = SEQ ID NO: 670

(cetuximab)
light chain = SEQ ID NO: 226

anti-EGFR-CD70ecd-PD1ecd
heavy chain = SEQ ID NO: 670

(cetuximab)
light chain = SEQ ID NO: 221

anti-EGFR-CD70ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 670

(cetuximab)
light chain = SEQ ID NO: 222

anti-EGFR-CD70ecd-SIRPaecd
heavy chain = SEQ ID NO: 670

(cetuximab)
light chain = SEQ ID NO: 223

anti-EGFR-CD70ecd-TIM3ecd
heavy chain = SEQ ID NO: 670

(cetuximab)
light chain = SEQ ID NO: 224

anti-EGFR-GITRLecd
heavy chain = SEQ ID NO: 671

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFR-GITRLecd-BTLAecd
heavy chain = SEQ ID NO: 671

(cetuximab)
light chain = SEQ ID NO: 226

anti-EGFR-GITRLecd-PD1ecd
heavy chain = SEQ ID NO: 671

(cetuximab)
light chain = SEQ ID NO: 221

anti-EGFR-GITRLecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 671

(cetuximab)
light chain = SEQ ID NO: 222

anti-EGFR-GITRLecd-SIRPaecd
heavy chain = SEQ ID NO: 671

(cetuximab)
light chain = SEQ ID NO: 223

anti-EGFR-GITRLecd-TIM3ecd
heavy chain = SEQ ID NO: 671

(cetuximab)
light chain = SEQ ID NO: 224

anti-EGFR-ICOSLecd
heavy chain = SEQ ID NO: 672

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFR-ICOSLecd-BTLAecd
heavy chain = SEQ ID NO: 672

(cetuximab)
light chain = SEQ ID NO: 226

anti-EGFR-ICOSLecd-PD1ecd
heavy chain = SEQ ID NO: 672

(cetuximab)
light chain = SEQ ID NO: 221

anti-EGFR-ICOSLecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 672

(cetuximab)
light chain = SEQ ID NO: 222

anti-EGFR-ICOSLecd-SIRPaecd
heavy chain = SEQ ID NO: 672

(cetuximab)
light chain = SEQ ID NO: 223

anti-EGFR-ICOSLecd-TIM3ecd
heavy chain = SEQ ID NO: 672

(cetuximab)
light chain = SEQ ID NO: 224

anti-EGFR-IL12ecd
heavy chain = SEQ ID NO: 673

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFR-IL12ecd-BTLAecd
heavy chain = SEQ ID NO: 673

(cetuximab)
light chain = SEQ ID NO: 226

anti-EGFR-IL12ecd-PD1ecd
heavy chain = SEQ ID NO: 673

(cetuximab)
light chain = SEQ ID NO: 221

anti-EGFR-IL12ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 673

(cetuximab)
light chain = SEQ ID NO: 222

anti-EGFR-IL12ecd-SIRPaecd
heavy chain = SEQ ID NO: 673

(cetuximab)
light chain = SEQ ID NO: 223

anti-EGFR-IL12ecd-TIM3ecd
heavy chain = SEQ ID NO: 673

(cetuximab)
light chain = SEQ ID NO: 224

anti-EGFR-IL15ecd
heavy chain = SEQ ID NO: 674

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFR-IL15ecd-BTLAecd
heavy chain = SEQ ID NO: 674

(cetuximab)
light chain = SEQ ID NO: 226

anti-EGFR-IL15ecd-PD1ecd
heavy chain = SEQ ID NO: 674

(cetuximab)
light chain = SEQ ID NO: 221

anti-EGFR-IL15ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 674

(cetuximab)
light chain = SEQ ID NO: 222

anti-EGFR-IL15ecd-SIRPaecd
heavy chain = SEQ ID NO: 674

(cetuximab)
light chain = SEQ ID NO: 223

anti-EGFR-IL15ecd-TIM3ecd
heavy chain = SEQ ID NO: 674

(cetuximab)
light chain = SEQ ID NO: 224

anti-EGFR-LIGHTecd
heavy chain = SEQ ID NO: 675

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFR-LIGHTecd-BTLAecd
heavy chain = SEQ ID NO: 675

(cetuximab)
light chain = SEQ ID NO: 226

anti-EGFR-LIGHTecd-PD1ecd
heavy chain = SEQ ID NO: 675

(cetuximab)
light chain = SEQ ID NO: 221

anti-EGFR-LIGHTecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 675

(cetuximab)
light chain = SEQ ID NO: 222

anti-EGFR-LIGHTecd-SIRPaecd
heavy chain = SEQ ID NO: 675

(cetuximab)
light chain = SEQ ID NO: 223

anti-EGFR-LIGHTecd-TIM3ecd
heavy chain = SEQ ID NO: 675

(cetuximab)
light chain = SEQ ID NO: 224

anti-EGFR-OX40Lecd
heavy chain = SEQ ID NO: 676

(cetuximab)
light chain = SEQ ID NO: 43

anti-EGFR-OX40Lecd-BTLAecd
heavy chain = SEQ ID NO: 676

(cetuximab)
light chain = SEQ ID NO: 226

anti-EGFR-OX40Lecd-PD1ecd
heavy chain = SEQ ID NO: 676

(cetuximab)
light chain = SEQ ID NO: 221

anti-EGFR-OX40Lecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 676

(cetuximab)
light chain = SEQ ID NO: 222

anti-EGFR-OX40Lecd-SIRPaecd
heavy chain = SEQ ID NO: 676

(cetuximab)
light chain = SEQ ID NO: 223

anti-EGFR-OX40Lecd-TIM3ecd
heavy chain = SEQ ID NO: 676

(cetuximab)
light chain = SEQ ID NO: 224

anti-EGFR-BTLAecd-41BBLecd
heavy chain = SEQ ID NO: 220

(cetuximab)
light chain = SEQ ID NO: 677

anti-EGFR-BTLAecd-CD30Lecd
heavy chain = SEQ ID NO: 220

(cetuximab)
light chain = SEQ ID NO: 678

anti-EGFR-BTLAecd-CD40Lecd
heavy chain = SEQ ID NO: 220

(cetuximab)
light chain = SEQ ID NO: 679

anti-EGFR-BTLAecd-CD70ecd
heavy chain = SEQ ID NO: 220

(cetuximab)
light chain = SEQ ID NO: 680

anti-EGFR-BTLAecd-GITRLecd
heavy chain = SEQ ID NO: 220

(cetuximab)
light chain = SEQ ID NO: 681

anti-EGFR-BTLAecd-ICOSLecd
heavy chain = SEQ ID NO: 220

(cetuximab)
light chain = SEQ ID NO: 682

anti-EGFR-BTLAecd-IL12ecd
heavy chain = SEQ ID NO: 220

(cetuximab)
light chain = SEQ ID NO: 683

anti-EGFR-BTLAecd-IL15ecd
heavy chain = SEQ ID NO: 220

(cetuximab)
light chain = SEQ ID NO: 684

anti-EGFR-BTLAecd-LIGHTecd
heavy chain = SEQ ID NO: 220

(cetuximab)
light chain = SEQ ID NO: 685

anti-EGFR-BTLAecd-OX40Lecd
heavy chain = SEQ ID NO: 220

(cetuximab)
light chain = SEQ ID NO: 686

anti-EGFR-PD1ecd-41BBLecd
heavy chain = SEQ ID NO: 225

(cetuximab)
light chain = SEQ ID NO: 677

anti-EGFR-PD1ecd-CD30Lecd
heavy chain = SEQ ID NO: 225

(cetuximab)
light chain = SEQ ID NO: 678

anti-EGFR-PD1ecd-CD40Lecd
heavy chain = SEQ ID NO: 225

(cetuximab)
light chain = SEQ ID NO: 679

anti-EGFR-PD1ecd-CD70ecd
heavy chain = SEQ ID NO: 225

(cetuximab)
light chain = SEQ ID NO: 680

anti-EGFR-PD1ecd-GITRLecd
heavy chain = SEQ ID NO: 225

(cetuximab)
light chain = SEQ ID NO: 681

anti-EGFR-PD1ecd-ICOSLecd
heavy chain = SEQ ID NO: 225

(cetuximab)
light chain = SEQ ID NO: 682

anti-EGFR-PD1ecd-IL12ecd
heavy chain = SEQ ID NO: 225

(cetuximab)
light chain = SEQ ID NO: 683

anti-EGFR-PD1ecd-IL15ecd
heavy chain = SEQ ID NO: 225

(cetuximab)
light chain = SEQ ID NO: 684

anti-EGFR-PD1ecd-LIGHTecd
heavy chain = SEQ ID NO: 225

(cetuximab)
light chain = SEQ ID NO: 685

anti-EGFR-PD1ecd-OX40Lecd
heavy chain = SEQ ID NO: 225

(cetuximab)
light chain = SEQ ID NO: 686

anti-EGFR-SIGLEC10ecd-41BBLecd
heavy chain = SEQ ID NO: 227

(cetuximab)
light chain = SEQ ID NO: 677

anti-EGFR-SIGLEC10ecd-CD30Lecd
heavy chain = SEQ ID NO: 227

(cetuximab)
light chain = SEQ ID NO: 678

anti-EGFR-SIGLEC10ecd-CD40Lecd
heavy chain = SEQ ID NO: 227

(cetuximab)
light chain = SEQ ID NO: 679

anti-EGFR-SIGLEC10ecd-CD70ecd
heavy chain = SEQ ID NO: 227

(cetuximab)
light chain = SEQ ID NO: 680

anti-EGFR-SIGLEC10ecd-GITRLecd
heavy chain = SEQ ID NO: 227

(cetuximab)
light chain = SEQ ID NO: 681

anti-EGFR-SIGLEC10ecd-ICOSLecd
heavy chain = SEQ ID NO: 227

(cetuximab)
light chain = SEQ ID NO: 682

anti-EGFR-SIGLEC10ecd-IL12ecd
heavy chain = SEQ ID NO: 227

(cetuximab)
light chain = SEQ ID NO: 683

anti-EGFR-SIGLEC10ecd-IL15ecd
heavy chain = SEQ ID NO: 227

(cetuximab)
light chain = SEQ ID NO: 684

anti-EGFR-SIGLEC10ecd-LIGHTecd
heavy chain = SEQ ID NO: 227

(cetuximab)
light chain = SEQ ID NO: 685

anti-EGFR-SIGLEC10ecd-OX40Lecd
heavy chain = SEQ ID NO: 227

(cetuximab)
light chain = SEQ ID NO: 686

anti-EGFR-SIRPaecd-41BBLecd
heavy chain = SEQ ID NO: 228

(cetuximab)
light chain = SEQ ID NO: 677

anti-EGFR-SIRPaecd-CD30Lecd
heavy chain = SEQ ID NO: 228

(cetuximab)
light chain = SEQ ID NO: 678

anti-EGFR-SIRPaecd-CD40Lecd
heavy chain = SEQ ID NO: 228

(cetuximab)
light chain = SEQ ID NO: 679

anti-EGFR-SIRPaecd-CD70ecd
heavy chain = SEQ ID NO: 228

(cetuximab)
light chain = SEQ ID NO: 680

anti-EGFR-SIRPaecd-GITRLecd
heavy chain = SEQ ID NO: 228

(cetuximab)
light chain = SEQ ID NO: 681

anti-EGFR-SIRPaecd-ICOSLecd
heavy chain = SEQ ID NO: 228

(cetuximab)
light chain = SEQ ID NO: 682

anti-EGFR-SIRPaecd-IL12ecd
heavy chain = SEQ ID NO: 228

(cetuximab)
light chain = SEQ ID NO: 683

anti-EGFR-SIRPaecd-IL15ecd
heavy chain = SEQ ID NO: 228

(cetuximab)
light chain = SEQ ID NO: 684

anti-EGFR-SIRPaecd-LIGHTecd
heavy chain = SEQ ID NO: 228

(cetuximab)
light chain = SEQ ID NO: 685

anti-EGFR-SIRPaecd-OX40Lecd
heavy chain = SEQ ID NO: 228

(cetuximab)
light chain = SEQ ID NO: 686

anti-EGFR-TGFbRecd-41BBLecd
heavy chain = SEQ ID NO: 229

(cetuximab)
light chain = SEQ ID NO: 677

anti-EGFR-TGFbRecd-CD30Lecd
heavy chain = SEQ ID NO: 229

(cetuximab)
light chain = SEQ ID NO: 678

anti-EGFR-TGFbRecd-CD40Lecd
heavy chain = SEQ ID NO: 229

(cetuximab)
light chain = SEQ ID NO: 679

anti-EGFR-TGFbRecd-CD70ecd
heavy chain = SEQ ID NO: 229

(cetuximab)
light chain = SEQ ID NO: 680

anti-EGFR-TGFbRecd-GITRLecd
heavy chain = SEQ ID NO: 229

(cetuximab)
light chain = SEQ ID NO: 681

anti-EGFR-TGFbRecd-ICOSLecd
heavy chain = SEQ ID NO: 229

(cetuximab)
light chain = SEQ ID NO: 682

anti-EGFR-TGFbRecd-IL12ecd
heavy chain = SEQ ID NO: 229

(cetuximab)
light chain = SEQ ID NO: 683

anti-EGFR-TGFbRecd-IL15ecd
heavy chain = SEQ ID NO: 229

(cetuximab)
light chain = SEQ ID NO: 684

anti-EGFR-TGFbRecd-LIGHTecd
heavy chain = SEQ ID NO: 229

(cetuximab)
light chain = SEQ ID NO: 685

anti-EGFR-TGFbRecd-OX40Lecd
heavy chain = SEQ ID NO: 229

(cetuximab)
light chain = SEQ ID NO: 686

anti-EGFR-TIM3ecd-41BBLecd
heavy chain = SEQ ID NO: 230

(cetuximab)
light chain = SEQ ID NO: 677

anti-EGFR-TIM3ecd-CD30Lecd
heavy chain = SEQ ID NO: 230

(cetuximab)
light chain = SEQ ID NO: 678

anti-EGFR-TIM3ecd-CD40Lecd
heavy chain = SEQ ID NO: 230

(cetuximab)
light chain = SEQ ID NO: 679

anti-EGFR-TIM3ecd-CD70ecd
heavy chain = SEQ ID NO: 230

(cetuximab)
light chain = SEQ ID NO: 680

anti-EGFR-TIM3ecd-GITRLecd
heavy chain = SEQ ID NO: 230

(cetuximab)
light chain = SEQ ID NO: 681

anti-EGFR-TIM3ecd-ICOSLecd
heavy chain = SEQ ID NO: 230

(cetuximab)
light chain = SEQ ID NO: 682

anti-EGFR-TIM3ecd-IL12ecd
heavy chain = SEQ ID NO: 230

(cetuximab)
light chain = SEQ ID NO: 683

anti-EGFR-TIM3ecd-IL15ecd
heavy chain = SEQ ID NO: 230

(cetuximab)
light chain = SEQ ID NO: 684

anti-EGFR-TIM3ecd-LIGHTecd
heavy chain = SEQ ID NO: 230

(cetuximab)
light chain = SEQ ID NO: 685

anti-EGFR-TIM3ecd-OX40Lecd
heavy chain = SEQ ID NO: 230

(cetuximab)
light chain = SEQ ID NO: 686

anti-EGFR-VEGFRecd-41BBLecd
heavy chain = SEQ ID NO: 231

(cetuximab)
light chain = SEQ ID NO: 677

anti-EGFR-VEGFRecd-CD30Lecd
heavy chain = SEQ ID NO: 231

(cetuximab)
light chain = SEQ ID NO: 678

anti-EGFR-VEGFRecd-CD40Lecd
heavy chain = SEQ ID NO: 231

(cetuximab)
light chain = SEQ ID NO: 679

anti-EGFR-VEGFRecd-CD70ecd
heavy chain = SEQ ID NO: 231

(cetuximab)
light chain = SEQ ID NO: 680

anti-EGFR-VEGFRecd-GITRLecd
heavy chain = SEQ ID NO: 231

(cetuximab)
light chain = SEQ ID NO: 681

anti-EGFR-VEGFRecd-ICOSLecd
heavy chain = SEQ ID NO: 231

(cetuximab)
light chain = SEQ ID NO: 682

anti-EGFR-VEGFRecd-IL12ecd
heavy chain = SEQ ID NO: 231

(cetuximab)
light chain = SEQ ID NO: 683

anti-EGFR-VEGFRecd-IL15ecd
heavy chain = SEQ ID NO: 231

(cetuximab)
light chain = SEQ ID NO: 684

anti-EGFR-VEGFRecd-LIGHTecd
heavy chain = SEQ ID NO: 231

(cetuximab)
light chain = SEQ ID NO: 685

anti-EGFR-VEGFRecd-OX40Lecd
heavy chain = SEQ ID NO: 231

(cetuximab)
light chain = SEQ ID NO: 686

anti-IL17R-41BBLecd
heavy chain = SEQ ID NO: 687

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL17R-41BBLecd-BTLAecd
heavy chain = SEQ ID NO: 687

(brodalumab)
light chain = SEQ ID NO: 331

anti-IL17R-41BBLecd-PD1ecd
heavy chain = SEQ ID NO: 687

(brodalumab)
light chain = SEQ ID NO: 326

anti-IL17R-41BBLecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 687

(brodalumab)
light chain = SEQ ID NO: 327

anti-IL17R-41BBLecd-SIRPaecd
heavy chain = SEQ ID NO: 687

(brodalumab)
light chain = SEQ ID NO: 328

anti-IL17R-41BBLecd-TIM3ecd
heavy chain = SEQ ID NO: 687

(brodalumab)
light chain = SEQ ID NO: 329

anti-IL17R-CD30Lecd
heavy chain = SEQ ID NO: 688

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL17R-CD30Lecd-BTLAecd
heavy chain = SEQ ID NO: 688

(brodalumab)
light chain = SEQ ID NO: 331

anti-IL17R-CD30Lecd-PD1ecd
heavy chain = SEQ ID NO: 688

(brodalumab)
light chain = SEQ ID NO: 326

anti-IL17R-CD30Lecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 688

(brodalumab)
light chain = SEQ ID NO: 327

anti-IL17R-CD30Lecd-SIRPaecd
heavy chain = SEQ ID NO: 688

(brodalumab)
light chain = SEQ ID NO: 328

anti-IL17R-CD30Lecd-TIM3ecd
heavy chain = SEQ ID NO: 688

(brodalumab)
light chain = SEQ ID NO: 329

anti-IL17R-CD40Lecd
heavy chain = SEQ ID NO: 689

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL17R-CD40Lecd-BTLAecd
heavy chain = SEQ ID NO: 689

(brodalumab)
light chain = SEQ ID NO: 331

anti-IL17R-CD40Lecd-PD1ecd
heavy chain = SEQ ID NO: 689

(brodalumab)
light chain = SEQ ID NO: 326

anti-IL17R-CD40Lecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 689

(brodalumab)
light chain = SEQ ID NO: 327

anti-IL17R-CD40Lecd-SIRPaecd
heavy chain = SEQ ID NO: 689

(brodalumab)
light chain = SEQ ID NO: 328

anti-IL17R-CD40Lecd-TIM3ecd
heavy chain = SEQ ID NO: 689

(brodalumab)
light chain = SEQ ID NO: 329

anti-IL17R-CD70ecd
heavy chain = SEQ ID NO: 690

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL17R-CD70ecd-BTLAecd
heavy chain = SEQ ID NO: 690

(brodalumab)
light chain = SEQ ID NO: 331

anti-IL17R-CD70ecd-PD1ecd
heavy chain = SEQ ID NO: 690

(brodalumab
light chain = SEQ ID NO: 326

anti-IL17R-CD70ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 690

(brodalumab)
light chain = SEQ ID NO: 327

anti-IL17R-CD70ecd-SIRPaecd
heavy chain = SEQ ID NO: 690

(brodalumab)
light chain = SEQ ID NO: 328

anti-IL17R-CD70ecd-TIM3ecd
heavy chain = SEQ ID NO: 690

(brodalumab)
light chain = SEQ ID NO: 329

anti-IL17R-GITRLecd
heavy chain = SEQ ID NO: 691

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL17R-GITRLecd-BTLAecd
heavy chain = SEQ ID NO: 691

(brodalumab)
light chain = SEQ ID NO: 331

anti-IL17R-GITRLecd-PD1ecd
heavy chain = SEQ ID NO: 691

(brodalumab)
light chain = SEQ ID NO: 326

anti-IL17R-GITRLecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 691

(brodalumab)
light chain = SEQ ID NO: 327

anti-IL17R-GITRLecd-SIRPaecd
heavy chain = SEQ ID NO: 691

(brodalumab)
light chain = SEQ ID NO: 328

anti-IL17R-GITRLecd-TIM3ecd
heavy chain = SEQ ID NO: 691

(brodalumab)
light chain = SEQ ID NO: 329

anti-IL17R-ICOSLecd
heavy chain = SEQ ID NO: 692

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL17R-ICOSLecd-BTLAecd
heavy chain = SEQ ID NO: 692

(brodalumab)
light chain = SEQ ID NO: 331

anti-IL17R-ICOSLecd-PD1ecd
heavy chain = SEQ ID NO: 692

(brodalumab)
light chain = SEQ ID NO: 326

anti-IL17R-ICOSLecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 692

(brodalumab)
light chain = SEQ ID NO: 327

anti-IL17R-ICOSLecd-SIRPaecd
heavy chain = SEQ ID NO: 692

(brodalumab)
light chain = SEQ ID NO: 328

anti-IL17R-ICOSLecd-TIM3ecd
heavy chain = SEQ ID NO: 692

(brodalumab)
light chain = SEQ ID NO: 329

anti-IL17R-IL12ecd
heavy chain = SEQ ID NO: 693

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL17R-IL12ecd-BTLAecd
heavy chain = SEQ ID NO: 693

(brodalumab)
light chain = SEQ ID NO: 331

anti-IL17R-IL12ecd-PD1ecd
heavy chain = SEQ ID NO: 693

(brodalumab)
light chain = SEQ ID NO: 326

anti-IL17R-IL12ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 693

(brodalumab)
light chain = SEQ ID NO: 327

anti-IL17R-IL12ecd-SIRPaecd
heavy chain = SEQ ID NO: 693

(brodalumab)
light chain = SEQ ID NO: 328

anti-IL17R-IL12ecd-TIM3ecd
heavy chain = SEQ ID NO: 693

(brodalumab)
light chain = SEQ ID NO: 329

anti-IL17R-IL15ecd
heavy chain = SEQ ID NO: 694

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL17R-IL15ecd-BTLAecd
heavy chain = SEQ ID NO: 694

(brodalumab)
light chain = SEQ ID NO: 331

anti-IL17R-IL15ecd-PD1ecd
heavy chain = SEQ ID NO: 694

(brodalumab)
light chain = SEQ ID NO: 326

anti-IL17R-IL15ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 694

(brodalumab)
light chain = SEQ ID NO: 327

anti-IL17R-IL15ecd-SIRPaecd
heavy chain = SEQ ID NO: 694

(brodalumab)
light chain = SEQ ID NO: 328

anti-IL17R-IL15ecd-TIM3ecd
heavy chain = SEQ ID NO: 694

(brodalumab)
light chain = SEQ ID NO: 329

anti-IL17R-LIGHTecd
heavy chain = SEQ ID NO: 695

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL17R-LIGHTecd-BTLAecd
heavy chain = SEQ ID NO: 695

(brodalumab)
light chain = SEQ ID NO: 331

anti-IL17R-LIGHTecd-PD1ecd
heavy chain = SEQ ID NO: 695

(brodalumab)
light chain = SEQ ID NO: 326

anti-IL17R-LIGHTecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 695

(brodalumab)
light chain = SEQ ID NO: 327

anti-IL17R-LIGHTecd-SIRPaecd
heavy chain = SEQ ID NO: 695

(brodalumab)
light chain = SEQ ID NO: 328

anti-IL17R-LIGHTecd-TIM3ecd
heavy chain = SEQ ID NO: 695

(brodalumab)
light chain = SEQ ID NO: 329

anti-IL17R-OX40Lecd
heavy chain = SEQ ID NO: 696

(brodalumab)
light chain = SEQ ID NO: 63

anti-IL17R-OX40Lecd-BTLAecd
heavy chain = SEQ ID NO: 696

(brodalumab)
light chain = SEQ ID NO: 331

anti-IL17R-OX40Lecd-PD1ecd
heavy chain = SEQ ID NO: 696

(brodalumab)
light chain = SEQ ID NO: 326

anti-IL17R-OX40Lecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 696

(brodalumab)
light chain = SEQ ID NO: 327

anti-IL17R-OX40Lecd-SIRPaecd
heavy chain = SEQ ID NO: 696

(brodalumab)
light chain = SEQ ID NO: 328

anti-IL17R-OX40Lecd-TIM3ecd
heavy chain = SEQ ID NO: 696

(brodalumab)
light chain = SEQ ID NO: 329

anti-IL17R-BTLAecd-41BBLecd
heavy chain = SEQ ID NO: 325

(brodalumab)
light chain = SEQ ID NO: 697

anti-IL17R-BTLAecd-CD30Lecd
heavy chain = SEQ ID NO: 325

(brodalumab)
light chain = SEQ ID NO: 698

anti-IL17R-BTLAecd-CD40Lecd
heavy chain = SEQ ID NO: 325

(brodalumab)
light chain = SEQ ID NO: 699

anti-IL17R-BTLAecd-CD70ecd
heavy chain = SEQ ID NO: 325

(brodalumab)
light chain = SEQ ID NO: 700

anti-IL17R-BTLAecd-GITRLecd
heavy chain = SEQ ID NO: 325

(brodalumab)
light chain = SEQ ID NO: 701

anti-IL17R-BTLAecd-ICOSLecd
heavy chain = SEQ ID NO: 325

(brodalumab)
light chain = SEQ ID NO: 702

anti-IL17R-BTLAecd-IL12ecd
heavy chain = SEQ ID NO: 325

(brodalumab)
light chain = SEQ ID NO: 703

anti-IL17R-BTLAecd-IL15ecd
heavy chain = SEQ ID NO: 325

(brodalumab)
light chain = SEQ ID NO: 704

anti-IL17R-BTLAecd-LIGHTecd
heavy chain = SEQ ID NO: 325

(brodalumab)
light chain = SEQ ID NO: 705

anti-IL17R-BTLAecd-OX40Lecd
heavy chain = SEQ ID NO: 325

(brodalumab)
light chain = SEQ ID NO: 706

anti-IL17R-PD1ecd-41BBLecd
heavy chain = SEQ ID NO: 330

(brodalumab)
light chain = SEQ ID NO: 697

anti-IL17R-PD1ecd-CD30Lecd
heavy chain = SEQ ID NO: 330

(brodalumab)
light chain = SEQ ID NO: 698

anti-IL17R-PD1ecd-CD40Lecd
heavy chain = SEQ ID NO: 330

(brodalumab)
light chain = SEQ ID NO: 699

anti-IL17R-PD1ecd-CD70ecd
heavy chain = SEQ ID NO: 330

(brodalumab)
light chain = SEQ ID NO: 700

anti-IL17R-PD1ecd-GITRLecd
heavy chain = SEQ ID NO: 330

(brodalumab)
light chain = SEQ ID NO: 701

anti-IL17R-PD1ecd-ICOSLecd
heavy chain = SEQ ID NO: 330

(brodalumab)
light chain = SEQ ID NO: 702

anti-IL17R-PD1ecd-IL12ecd
heavy chain = SEQ ID NO: 330

(brodalumab)
light chain = SEQ ID NO: 703

anti-IL17R-PD1ecd-IL15ecd
heavy chain = SEQ ID NO: 330

(brodalumab)
light chain = SEQ ID NO: 704

anti-IL17R-PD1ecd-LIGHTecd
heavy chain = SEQ ID NO: 330

(brodalumab)
light chain = SEQ ID NO: 705

anti-IL17R-PD1ecd-OX40Lecd
heavy chain = SEQ ID NO: 330

(brodalumab)
light chain = SEQ ID NO: 706

anti-IL17R-SIGLEC10ecd-41BBLecd
heavy chain = SEQ ID NO: 332

(brodalumab)
light chain = SEQ ID NO: 697

anti-IL17R-SIGLEC10ecd-CD30Lecd
heavy chain = SEQ ID NO: 332

(brodalumab)
light chain = SEQ ID NO: 698

anti-IL17R-SIGLEC10ecd-CD40Lecd
heavy chain = SEQ ID NO: 332

(brodalumab)
light chain = SEQ ID NO: 699

anti-IL17R-SIGLEC10ecd-CD70ecd
heavy chain = SEQ ID NO: 332

(brodalumab)
light chain = SEQ ID NO: 700

anti-IL17R-SIGLEC10ecd-GITRLecd
heavy chain = SEQ ID NO: 332

(brodalumab)
light chain = SEQ ID NO: 701

anti-IL17R-SIGLEC10ecd-ICOSLecd
heavy chain = SEQ ID NO: 332

(brodalumab)
light chain = SEQ ID NO: 702

anti-IL17R-SIGLEC10ecd-IL12ecd
heavy chain = SEQ ID NO: 332

(brodalumab)
light chain = SEQ ID NO: 703

anti-IL17R-SIGLEC10ecd-IL15ecd
heavy chain = SEQ ID NO: 332

(brodalumab)
light chain = SEQ ID NO: 704

anti-IL17R-SIGLEC10ecd-LIGHTecd
heavy chain = SEQ ID NO: 332

(brodalumab)
light chain = SEQ ID NO: 705

anti-IL17R-SIGLEC10ecd-OX40Lecd
heavy chain = SEQ ID NO: 332

(brodalumab)
light chain = SEQ ID NO: 706

anti-IL17R-SIRPaecd-41BBLecd
heavy chain = SEQ ID NO: 333

(brodalumab)
light chain = SEQ ID NO: 697

anti-IL17R-SIRPaecd-CD30Lecd
heavy chain = SEQ ID NO: 333

(brodalumab)
light chain = SEQ ID NO: 698

anti-IL17R-SIRPaecd-CD40Lecd
heavy chain = SEQ ID NO: 333

(brodalumab)
light chain = SEQ ID NO: 699

anti-IL17R-SIRPaecd-CD70ecd
heavy chain = SEQ ID NO: 333

(brodalumab)
light chain = SEQ ID NO: 700

anti-IL17R-SIRPaecd-GITRLecd
heavy chain = SEQ ID NO: 333

(brodalumab)
light chain = SEQ ID NO: 701

anti-IL17R-SIRPaecd-ICOSLecd
heavy chain = SEQ ID NO: 333

(brodalumab)
light chain = SEQ ID NO: 702

anti-IL17R-SIRPaecd-IL12ecd
heavy chain = SEQ ID NO: 333

(brodalumab)
light chain = SEQ ID NO: 703

anti-IL17R-SIRPaecd-IL15ecd
heavy chain = SEQ ID NO: 333

(brodalumab)
light chain = SEQ ID NO: 704

anti-IL17R-SIRPaecd-LIGHTecd
heavy chain = SEQ ID NO: 333

(brodalumab)
light chain = SEQ ID NO: 705

anti-IL17R-SIRPaecd-OX40Lecd
heavy chain = SEQ ID NO: 333

(brodalumab)
light chain = SEQ ID NO: 706

anti-IL17R-TGFbRecd-41BBLecd
heavy chain = SEQ ID NO: 334

(brodalumab)
light chain = SEQ ID NO: 697

anti-IL17R-TGFbRecd-CD30Lecd
heavy chain = SEQ ID NO: 334

(brodalumab)
light chain = SEQ ID NO: 698

anti-IL17R-TGFbRecd-CD40Lecd
heavy chain = SEQ ID NO: 334

(brodalumab)
light chain = SEQ ID NO: 699

anti-IL17R-TGFbRecd-CD70ecd
heavy chain = SEQ ID NO: 334

(brodalumab)
light chain = SEQ ID NO: 700

anti-IL17R-TGFbRecd-GITRLecd
heavy chain = SEQ ID NO: 334

(brodalumab)
light chain = SEQ ID NO: 701

anti-IL17R-TGFbRecd-ICOSLecd
heavy chain = SEQ ID NO: 334

(brodalumab)
light chain = SEQ ID NO: 702

anti-IL17R-TGFbRecd-IL12ecd
heavy chain = SEQ ID NO: 334

(brodalumab)
light chain = SEQ ID NO: 703

anti-IL17R-TGFbRecd-IL15ecd
heavy chain = SEQ ID NO: 334

(brodalumab)
light chain = SEQ ID NO: 704

anti-IL17R-TGFbRecd-LIGHTecd
heavy chain = SEQ ID NO: 334

(brodalumab)
light chain = SEQ ID NO: 705

anti-IL17R-TGFbRecd-OX40Lecd
heavy chain = SEQ ID NO: 334

(brodalumab)
light chain = SEQ ID NO: 706

anti-IL17R-TIM3ecd-41BBLecd
heavy chain = SEQ ID NO: 335

(brodalumab)
light chain = SEQ ID NO: 697

anti-IL17R-TIM3ecd-CD30Lecd
heavy chain = SEQ ID NO: 335

(brodalumab)
light chain = SEQ ID NO: 698

anti-IL17R-TIM3ecd-CD40Lecd
heavy chain = SEQ ID NO: 335

(brodalumab)
light chain = SEQ ID NO: 699

anti-IL17R-TIM3ecd-CD70ecd
heavy chain = SEQ ID NO: 335

(brodalumab)
light chain = SEQ ID NO: 700

anti-IL17R-TIM3ecd-GITRLecd
heavy chain = SEQ ID NO: 335

(brodalumab)
light chain = SEQ ID NO: 701

anti-IL17R-TIM3ecd-ICOSLecd
heavy chain = SEQ ID NO: 335

(brodalumab)
light chain = SEQ ID NO: 702

anti-IL17R-TIM3ecd-IL12ecd
heavy chain = SEQ ID NO: 335

(brodalumab)
light chain = SEQ ID NO: 703

anti-IL17R-TIM3ecd-IL15ecd
heavy chain = SEQ ID NO: 335

(brodalumab)
light chain = SEQ ID NO: 704

anti-IL17R-TIM3ecd-LIGHTecd
heavy chain = SEQ ID NO: 335

(brodalumab)
light chain = SEQ ID NO: 705

anti-IL17R-TIM3ecd-OX40Lecd
heavy chain = SEQ ID NO: 335

(brodalumab)
light chain = SEQ ID NO: 706

anti-IL17R-VEGFRecd-41BBLecd
heavy chain = SEQ ID NO: 336

(brodalumab)
light chain = SEQ ID NO: 697

anti-IL17R-VEGFRecd-CD30Lecd
heavy chain = SEQ ID NO: 336

(brodalumab)
light chain = SEQ ID NO: 698

anti-IL17R-VEGFRecd-CD40Lecd
heavy chain = SEQ ID NO: 336

(brodalumab)
light chain = SEQ ID NO: 699

anti-IL17R-VEGFRecd-CD70ecd
heavy chain = SEQ ID NO: 336

(brodalumab)
light chain = SEQ ID NO: 700

anti-IL17R-VEGFRecd-GITRLecd
heavy chain = SEQ ID NO: 336

(brodalumab)
light chain = SEQ ID NO: 701

anti-IL17R-VEGFRecd-ICOSLecd
heavy chain = SEQ ID NO: 336

(brodalumab)
light chain = SEQ ID NO: 702

anti-IL17R-VEGFRecd-IL12ecd
heavy chain = SEQ ID NO: 336

(brodalumab)
light chain = SEQ ID NO: 703

anti-IL17R-VEGFRecd-IL15ecd
heavy chain = SEQ ID NO: 336

(brodalumab)
light chain = SEQ ID NO: 704

anti-IL17R-VEGFRecd-LIGHTecd
heavy chain = SEQ ID NO: 336

(brodalumab)
light chain = SEQ ID NO: 705

anti-IL17R-VEGFRecd-OX40Lecd
heavy chain = SEQ ID NO: 336

(brodalumab)
light chain = SEQ ID NO: 706

anti-VEGF-41BBLecd
heavy chain = SEQ ID NO: 707

(bevacizumab)
light chain = SEQ ID NO: 32

anti-VEGF-41BBLecd-BTLAecd
heavy chain = SEQ ID NO: 707

(bevacizumab)
light chain = SEQ ID NO: 367

anti-VEGF-41BBLecd-PD1ecd
heavy chain = SEQ ID NO: 707

(bevacizumab)
light chain = SEQ ID NO: 362

anti-VEGF-41BBLecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 707

(bevacizumab)
light chain = SEQ ID NO: 363

anti-VEGF-41BBLecd-SIRPaecd
heavy chain = SEQ ID NO: 707

(bevacizumab)
light chain = SEQ ID NO: 364

anti-VEGF-41BBLecd-TIM3ecd
heavy chain = SEQ ID NO: 707

(bevacizumab)
light chain = SEQ ID NO: 365

anti-VEGF-CD30Lecd
heavy chain = SEQ ID NO: 708

(bevacizumab)
light chain = SEQ ID NO: 32

anti-VEGF-CD30Lecd-BTLAecd
heavy chain = SEQ ID NO: 708

(bevacizumab)
light chain = SEQ ID NO: 367

anti-VEGF-CD30Lecd-PD1ecd
heavy chain = SEQ ID NO: 708

(bevacizumab)
light chain = SEQ ID NO: 362

anti-VEGF-CD30Lecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 708

(bevacizumab)
light chain = SEQ ID NO: 363

anti-VEGF-CD30Lecd-SIRPaecd
heavy chain = SEQ ID NO: 708

(bevacizumab)
light chain = SEQ ID NO: 364

anti-VEGF-CD30Lecd-TIM3ecd
heavy chain = SEQ ID NO: 708

(bevacizumab)
light chain = SEQ ID NO: 365

anti-VEGF-CD40Lecd
heavy chain = SEQ ID NO: 709

(bevacizumab)
light chain = SEQ ID NO: 32

anti-VEGF-CD40Lecd-BTLAecd
heavy chain = SEQ ID NO: 709

(bevacizumab)
light chain = SEQ ID NO: 367

anti-VEGF-CD40Lecd-PD1ecd
heavy chain = SEQ ID NO: 709

(bevacizumab)
light chain = SEQ ID NO: 362

anti-VEGF-CD40Lecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 709

(bevacizumab)
light chain = SEQ ID NO: 363

anti-VEGF-CD40Lecd-SIRPaecd
heavy chain = SEQ ID NO: 709

(bevacizumab)
light chain = SEQ ID NO: 364

anti-VEGF-CD40Lecd-TIM3ecd
heavy chain = SEQ ID NO: 709

(bevacizumab)
light chain = SEQ ID NO: 365

anti-VEGF-CD70ecd
heavy chain = SEQ ID NO: 710

(bevacizumab)
light chain = SEQ ID NO: 32

anti-VEGF-CD70ecd-BTLAecd
heavy chain = SEQ ID NO: 710

(bevacizumab)
light chain = SEQ ID NO: 367

anti-VEGF-CD70ecd-PD1ecd
heavy chain = SEQ ID NO: 710

(bevacizumab)
light chain = SEQ ID NO: 362

anti-VEGF-CD70ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 710

(bevacizumab)
light chain = SEQ ID NO: 363

anti-VEGF-CD70ecd-SIRPaecd
heavy chain = SEQ ID NO: 710

(bevacizumab)
light chain = SEQ ID NO: 364

anti-VEGF-CD70ecd-TIM3ecd
heavy chain = SEQ ID NO: 710

(bevacizumab)
light chain = SEQ ID NO: 365

anti-VEGF-GITRLecd
heavy chain = SEQ ID NO: 711

(bevacizumab)
light chain = SEQ ID NO: 32

anti-VEGF-GITRLecd-BTLAecd
heavy chain = SEQ ID NO: 711

(bevacizumab)
light chain = SEQ ID NO: 367

anti-VEGF-GITRLecd-PD1ecd
heavy chain = SEQ ID NO: 711

(bevacizumab)
light chain = SEQ ID NO: 362

anti-VEGF-GITRLecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 711

(bevacizumab)
light chain = SEQ ID NO: 363

anti-VEGF-GITRLecd-SIRPaecd
heavy chain = SEQ ID NO: 711

(bevacizumab)
light chain = SEQ ID NO: 364

anti-VEGF-GITRLecd-TIM3ecd
heavy chain = SEQ ID NO: 711

(bevacizumab)
light chain = SEQ ID NO: 365

anti-VEGF-ICOSLecd
heavy chain = SEQ ID NO: 712

(bevacizumab)
light chain = SEQ ID NO: 32

anti-VEGF-ICOSLecd-BTLAecd
heavy chain = SEQ ID NO: 712

(bevacizumab)
light chain = SEQ ID NO: 367

anti-VEGF-ICOSLecd-PD1ecd
heavy chain = SEQ ID NO: 712

(bevacizumab)
light chain = SEQ ID NO: 362

anti-VEGF-ICOSLecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 712

(bevacizumab)
light chain = SEQ ID NO: 363

anti-VEGF-ICOSLecd-SIRPaecd
heavy chain = SEQ ID NO: 712

(bevacizumab)
light chain = SEQ ID NO: 364

anti-VEGF-ICOSLecd-TIM3ecd
heavy chain = SEQ ID NO: 712

(bevacizumab)
light chain = SEQ ID NO: 365

anti-VEGF-IL12ecd
heavy chain = SEQ ID NO: 713

(bevacizumab)
light chain = SEQ ID NO: 32

anti-VEGF-IL12ecd-BTLAecd
heavy chain = SEQ ID NO: 713

(bevacizumab)
light chain = SEQ ID NO: 367

anti-VEGF-IL12ecd-PD1ecd
heavy chain = SEQ ID NO: 713

(bevacizumab)
light chain = SEQ ID NO: 362

anti-VEGF-IL12ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 713

(bevacizumab)
light chain = SEQ ID NO: 363

anti-VEGF-IL12ecd-SIRPaecd
heavy chain = SEQ ID NO: 713

(bevacizumab)
light chain = SEQ ID NO: 364

anti-VEGF-IL12ecd-TIM3ecd
heavy chain = SEQ ID NO: 713

(bevacizumab)
light chain = SEQ ID NO: 365

anti-VEGF-IL15ecd
heavy chain = SEQ ID NO: 714

(bevacizumab)
light chain = SEQ ID NO: 32

anti-VEGF-IL15ecd-BTLAecd
heavy chain = SEQ ID NO: 714

(bevacizumab)
light chain = SEQ ID NO: 367

anti-VEGF-IL15ecd-PD1ecd
heavy chain = SEQ ID NO: 714

(bevacizumab)
light chain = SEQ ID NO: 362

anti-VEGF-IL15ecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 714

(bevacizumab)
light chain = SEQ ID NO: 363

anti-VEGF-IL15ecd-SIRPaecd
heavy chain = SEQ ID NO: 714

(bevacizumab)
light chain = SEQ ID NO: 364

anti-VEGF-IL15ecd-TIM3ecd
heavy chain = SEQ ID NO: 714

(bevacizumab)
light chain = SEQ ID NO: 365

anti-VEGF-LIGHTecd
heavy chain = SEQ ID NO: 715

(bevacizumab)
light chain = SEQ ID NO: 32

anti-VEGF-LIGHTecd-BTLAecd
heavy chain = SEQ ID NO: 715

(bevacizumab)
light chain = SEQ ID NO: 367

anti-VEGF-LIGHTecd-PD1ecd
heavy chain = SEQ ID NO: 715

(bevacizumab)
light chain = SEQ ID NO: 362

anti-VEGF-LIGHTecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 715

(bevacizumab)
light chain = SEQ ID NO: 363

anti-VEGF-LIGHTecd-SIRPaecd
heavy chain = SEQ ID NO: 715

(bevacizumab)
light chain = SEQ ID NO: 364

anti-VEGF-LIGHTecd-TIM3ecd
heavy chain = SEQ ID NO: 715

(bevacizumab)
light chain = SEQ ID NO: 365

anti-VEGF-OX40Lecd
heavy chain = SEQ ID NO: 716

(bevacizumab)
light chain = SEQ ID NO: 32

anti-VEGF-OX40Lecd-BTLAecd
heavy chain = SEQ ID NO: 716

(bevacizumab)
light chain = SEQ ID NO: 367

anti-VEGF-OX40Lecd-PD1ecd
heavy chain = SEQ ID NO: 716

(bevacizumab)
light chain = SEQ ID NO: 362

anti-VEGF-OX40Lecd-SIGLEC10ecd
heavy chain = SEQ ID NO: 716

(bevacizumab)
light chain = SEQ ID NO: 363

anti-VEGF-OX40Lecd-SIRPaecd
heavy chain = SEQ ID NO: 716

(bevacizumab)
light chain = SEQ ID NO: 364

anti-VEGF-OX40Lecd-TIM3ecd
heavy chain = SEQ ID NO: 716

(bevacizumab)
light chain = SEQ ID NO: 365

anti-VEGF-BTLAecd-41BBLecd
heavy chain = SEQ ID NO: 361

(bevacizumab)
light chain = SEQ ID NO: 717

anti-VEGF-BTLAecd-CD30Lecd
heavy chain = SEQ ID NO: 361

(bevacizumab)
light chain = SEQ ID NO: 718

anti-VEGF-BTLAecd-CD40Lecd
heavy chain = SEQ ID NO: 361

(bevacizumab)
light chain = SEQ ID NO: 719

anti-VEGF-BTLAecd-CD70ecd
heavy chain = SEQ ID NO: 361

(bevacizumab)
light chain = SEQ ID NO: 720

anti-VEGF-BTLAecd-GITRLecd
heavy chain = SEQ ID NO: 361

(bevacizumab)
light chain = SEQ ID NO: 721

anti-VEGF-BTLAecd-ICOSLecd
heavy chain = SEQ ID NO: 361

(bevacizumab)
light chain = SEQ ID NO: 722

anti-VEGF-BTLAecd-IL12ecd
heavy chain = SEQ ID NO: 361

(bevacizumab)
light chain = SEQ ID NO: 723

anti-VEGF-BTLAecd-IL15ecd
heavy chain = SEQ ID NO: 361

(bevacizumab)
light chain = SEQ ID NO: 724

anti-VEGF-BTLAecd-LIGHTecd
heavy chain = SEQ ID NO: 361

(bevacizumab)
light chain = SEQ ID NO: 725

anti-VEGF-BTLAecd-OX40Lecd
heavy chain = SEQ ID NO: 361

(bevacizumab)
light chain = SEQ ID NO: 726

anti-VEGF-PD1ecd-41BBLecd
heavy chain = SEQ ID NO: 366

(bevacizumab)
light chain = SEQ ID NO: 717

anti-VEGF-PD1ecd-CD30Lecd
heavy chain = SEQ ID NO: 366

(bevacizumab)
light chain = SEQ ID NO: 718

anti-VEGF-PD1ecd-CD40Lecd
heavy chain = SEQ ID NO: 366

(bevacizumab)
light chain = SEQ ID NO: 719

anti-VEGF-PD1ecd-CD70ecd
heavy chain = SEQ ID NO: 366

(bevacizumab)
light chain = SEQ ID NO: 720

anti-VEGF-PD1ecd-GITRLecd
heavy chain = SEQ ID NO: 366

(bevacizumab)
light chain = SEQ ID NO: 721

anti-VEGF-PD1ecd-ICOSLecd
heavy chain = SEQ ID NO: 366

(bevacizumab)
light chain = SEQ ID NO: 722

anti-VEGF-PD1ecd-IL12ecd
heavy chain = SEQ ID NO: 366

(bevacizumab)
light chain = SEQ ID NO: 723

anti-VEGF-PD1ecd-IL15ecd
heavy chain = SEQ ID NO: 366

(bevacizumab)
light chain = SEQ ID NO: 724

anti-VEGF-PD1ecd-LIGHTecd
heavy chain = SEQ ID NO: 366

(bevacizumab)
light chain = SEQ ID NO: 725

anti-VEGF-PD1ecd-OX40Lecd
heavy chain = SEQ ID NO: 366

(bevacizumab)
light chain = SEQ ID NO: 726

anti-VEGF-SIGLEC10ecd-41BBLecd
heavy chain = SEQ ID NO: 368

(bevacizumab)
light chain = SEQ ID NO: 717

anti-VEGF-SIGLEC10ecd-CD30Lecd
heavy chain = SEQ ID NO: 368

(bevacizumab)
light chain = SEQ ID NO: 718

anti-VEGF-SIGLEC10ecd-CD40Lecd
heavy chain = SEQ ID NO: 368

(bevacizumab)
light chain = SEQ ID NO: 719

anti-VEGF-SIGLEC10ecd-CD70ecd
heavy chain = SEQ ID NO: 368

(bevacizumab)
light chain = SEQ ID NO: 720

anti-VEGF-SIGLEC10ecd-GITRLecd
heavy chain = SEQ ID NO: 368

(bevacizumab)
light chain = SEQ ID NO: 721

anti-VEGF-SIGLEC10ecd-ICOSLecd
heavy chain = SEQ ID NO: 368

(bevacizumab)
light chain = SEQ ID NO: 722

anti-VEGF-SIGLEC10ecd-IL12ecd
heavy chain = SEQ ID NO: 368

(bevacizumab)
light chain = SEQ ID NO: 723

anti-VEGF-SIGLEC10ecd-IL15ecd
heavy chain = SEQ ID NO: 368

(bevacizumab)
light chain = SEQ ID NO: 724

anti-VEGF-SIGLEC10ecd-LIGHTecd
heavy chain = SEQ ID NO: 368

(bevacizumab)
light chain = SEQ ID NO: 725

anti-VEGF-SIGLEC10ecd-OX40Lecd
heavy chain = SEQ ID NO: 368

(bevacizumab)
light chain = SEQ ID NO: 726

anti-VEGF-SIRPaecd-41BBLecd
heavy chain = SEQ ID NO: 369

(bevacizumab)
light chain = SEQ ID NO: 717

anti-VEGF-SIRPaecd-CD30Lecd
heavy chain = SEQ ID NO: 369

(bevacizumab)
light chain = SEQ ID NO: 718

anti-VEGF-SIRPaecd-CD40Lecd
heavy chain = SEQ ID NO: 369

(bevacizumab)
light chain = SEQ ID NO: 719

anti-VEGF-SIRPaecd-CD70ecd
heavy chain = SEQ ID NO: 369

(bevacizumab)
light chain = SEQ ID NO: 720

anti-VEGF-SIRPaecd-GITRLecd
heavy chain = SEQ ID NO: 369

(bevacizumab)
light chain = SEQ ID NO: 721

anti-VEGF-SIRPaecd-ICOSLecd
heavy chain = SEQ ID NO: 369

(bevacizumab)
light chain = SEQ ID NO: 722

anti-VEGF-SIRPaecd-IL12ecd
heavy chain = SEQ ID NO: 369

(bevacizumab)
light chain = SEQ ID NO: 723

anti-VEGF-SIRPaecd-IL15ecd
heavy chain = SEQ ID NO: 369

(bevacizumab)
light chain = SEQ ID NO: 724

anti-VEGF-SIRPaecd-LIGHTecd
heavy chain = SEQ ID NO: 369

(bevacizumab)
light chain = SEQ ID NO: 725

anti-VEGF-SIRPaecd-OX40Lecd
heavy chain = SEQ ID NO: 369

(bevacizumab)
light chain = SEQ ID NO: 726

anti-VEGF-TGFbRecd-41BBLecd
heavy chain = SEQ ID NO: 370

(bevacizumab)
light chain = SEQ ID NO: 717

anti-VEGF-TGFbRecd-CD30Lecd
heavy chain = SEQ ID NO: 370

(bevacizumab)
light chain = SEQ ID NO: 718

anti-VEGF-TGFbRecd-CD40Lecd
heavy chain = SEQ ID NO: 370

(bevacizumab)
light chain = SEQ ID NO: 719

anti-VEGF-TGFbRecd-CD70ecd
heavy chain = SEQ ID NO: 370

(bevacizumab)
light chain = SEQ ID NO: 720

anti-VEGF-TGFbRecd-GITRLecd
heavy chain = SEQ ID NO: 370

(bevacizumab)
light chain = SEQ ID NO: 721

anti-VEGF-TGFbRecd-ICOSLecd
heavy chain = SEQ ID NO: 370

(bevacizumab)
light chain = SEQ ID NO: 722

anti-VEGF-TGFbRecd-IL12ecd
heavy chain = SEQ ID NO: 370

(bevacizumab)
light chain = SEQ ID NO: 723

anti-VEGF-TGFbRecd-IL15ecd
heavy chain = SEQ ID NO: 370

(bevacizumab)
light chain = SEQ ID NO: 724

anti-VEGF-TGFbRecd-LIGHTecd
heavy chain = SEQ ID NO: 370

(bevacizumab)
light chain = SEQ ID NO: 725

anti-VEGF-TGFbRecd-OX40Lecd
heavy chain = SEQ ID NO: 370

(bevacizumab)
light chain = SEQ ID NO: 726

anti-VEGF-TIM3ecd-41BBLecd
heavy chain = SEQ ID NO: 371

(bevacizumab)
light chain = SEQ ID NO: 717

anti-VEGF-TIM3ecd-CD30Lecd
heavy chain = SEQ ID NO: 371

(bevacizumab)
light chain = SEQ ID NO: 718

anti-VEGF-TIM3ecd-CD40Lecd
heavy chain = SEQ ID NO: 371

(bevacizumab)
light chain = SEQ ID NO: 719

anti-VEGF-TIM3ecd-CD70ecd
heavy chain = SEQ ID NO: 371

(bevacizumab)
light chain = SEQ ID NO: 720

anti-VEGF-TIM3ecd-GITRLecd
heavy chain = SEQ ID NO: 371

(bevacizumab)
light chain = SEQ ID NO: 721

anti-VEGF-TIM3ecd-ICOSLecd
heavy chain = SEQ ID NO: 371

(bevacizumab)
light chain = SEQ ID NO: 722

anti-VEGF-TIM3ecd-IL12ecd
heavy chain = SEQ ID NO: 371

(bevacizumab)
light chain = SEQ ID NO: 723

anti-VEGF-TIM3ecd-IL15ecd
heavy chain = SEQ ID NO: 371

(bevacizumab)
light chain = SEQ ID NO: 724

anti-VEGF-TIM3ecd-LIGHTecd
heavy chain = SEQ ID NO: 371

(bevacizumab)
light chain = SEQ ID NO: 725

anti-VEGF-TIM3ecd-OX40Lecd
heavy chain = SEQ ID NO: 371

(bevacizumab)
light chain = SEQ ID NO: 726

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID NOs: 747, 748

to BTLA on HC
light chains = SEQ ID NOs: 218, 219

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID NOs: 216, 217

to BTLA on LC
light chains = SEQ ID NOs: 749, 219

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID NOs: 216, 217

to BTLA on LC
light chains = SEQ ID NOs: 218, 750

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID NOs: 751, 752

to PD1 onHC
light chains = SEQ ID NOs: 218, 219

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID NOs: 216, 217

to PD1 on LC
light chains = SEQ ID NOs: 753, 219

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID NOs: 216, 217

to PD1 on LC
light chains = SEQ ID NOs: 218, 754

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID NOs: 755, 756

to SIGLEC10 on HC
light chains = SEQ ID NOs: 218, 219

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID Nos: 216, 217

to SIGLEC10 on LC
light chains = SEQ ID Nos: 757, 219

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID NOs: 216, 217

to SIGLEC10 on LC
light chains = SEQ ID NOs: 218, 758

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID NOs: 759, 760

to SIRPa on HC
light chains = SEQ ID NOs: 218, 219

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID NOs: 216, 217

to SIRPa on LC
light chains = SEQ ID NOs: 761, 219

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID NOs: 216, 217

to SIRPa on LC
light chains = SEQ ID NOs: 218, 762

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID NOs: 763, 764

to TGFbR on HC
light chains = SEQ ID NOs: 218, 219

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID NOs: 765, 766

to TIM3 on HC
light chains = SEQ ID NOs: 218, 219

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID NOs: 216, 217

to TIM3 on LC
light chains = SEQ ID NOs: 767, 219

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID NOs: 216, 217

to TIM3 on LC
light chains = SEQ ID NOs: 218, 768

anti-CEACAM5/CD3 (cibisatamab) fused
heavy chains = SEQ ID NOs: 769, 770

to VEGFR on HC
light chains = SEQ ID NOs: 218, 219

anti-CD3/CD19 (blinatumomab) fused
SEQ ID NO: 727

to BTLA

anti-CD3/CD19 (blinatumomab) fused
SEQ ID NO: 728

to BTLA

anti-CD3/PSMA (pasotuxizumab) fused
SEQ ID NO: 729

to BTLA

anti-CD3/PSMA (pasotuxizumab) fused
SEQ ID NO: 730

to BTLA

anti-CD3/CD19 (blinatumomab) fused
SEQ ID NO: 731

to PD1

anti-CD3/CD19 (blinatumomab) fused
SEQ ID NO: 732

to PD1

anti-CD3/PSMA (pasotuxizumab) fused
SEQ ID NO: 733

to PD1

anti-CD3/PSMA (pasotuxizumab) fused
SEQ ID NO: 734

to PD1

anti-CD3/CD19 (blinatumomab) fused
SEQ ID NO: 735

to SIGLEC10

anti-CD3/CD19 (blinatumomab) fused
SEQ ID NO: 736

to SIGLEC10

anti-CD3/PSMA (pasotuxizumab) fused
SEQ ID NO: 737

to SIGLEC10

anti-CD3/PSMA (pasotuxizumab) fused
SEQ ID NO: 738

to SIGLEC10

anti-CD3/CD19 (blinatumomab) fused
SEQ ID NO: 739

to SIRPa

anti-CD3/CD19 (blinatumomab) fused
SEQ ID NO: 740

to SIRPa

anti-CD3/PSMA (pasotuxizumab) fused
SEQ ID NO: 741

to SIRPa

anti-CD3/PSMA (pasotuxizumab) fused
SEQ ID NO: 742

to SIRPa

anti-CD3/CD19 (blinatumomab) fused
SEQ ID NO: 743

to TIM3

anti-CD3/CD19 (blinatumomab) fused
SEQ ID NO: 744

to TIM3

anti-CD3/PSMA (pasotuxizumab) fused
SEQ ID NO: 745

to TIM3

anti-CD3/PSMA (pasotuxizumab) fused
SEQ ID NO: 746

to TIM3

The following examples are provided to further illustrate the embodiments of the present invention, but are not intended to limit the scope of the invention. While they are typical of those that might be used, other procedures, methodologies, or techniques known to those skilled in the art may alternatively be used.

EXAMPLES
Example 1
Methods

The amino acid sequences of exemplary fusion proteins of the invention were codon optimized with GeneOptimizer®. The cDNA for the antibody heavy chain and the cDNA for the antibody light chain were gene synthesized and subsequently cloned into separate plasmids (pEvi3; evitria AG, Switzerland) under the control of a mammalian promoter and polyadenylation signal. Plasmid DNA was amplified in E. coli and DNA was purified using anion exchange kits for low endotoxin plasmid DNA preparation. DNA concentration was determined by measuring the absorption at a wavelength of 260 nm. Correctness of the sequences was verified with Sanger sequencing (with up to two sequencing reactions per plasmid depending on the size of the cDNA.) The plasmid DNAs for heavy and light chain were subsequently co-transfected into suspension-adapted CHO K1 cells (originally received from ATCC and adapted to serum-free growth in suspension culture at evitria). The seed was grown in eviGrow medium, a chemically defined, animal-component free, serum-free medium. Cells were transfected with eviFect (evitria AG, Switzerland). and the CHO cells were cultured in eviMake2 (evitria AG, Switzerland), a serum-free, animal-component free medium. Production was terminated once viability reached 75%, which occurred at day 8 after transfection. Supernatant was harvested by centrifugation and subsequent filtration (0.2 um filter). The antibody was purified using MabSelect™ Sure™ (Protein A affinity chromatography on a Bio-Rad BioLogic FuoFlow FPLC machine with subsequent gel filtration as polishing and rebuffering step). In some cases, the antibody was further purified using SEC purification.

The fusion proteins of the invention can also be produced via stable transfection of a mammalian cell line (e.g. CHO K1 cells) with plasmid DNA encoding the chains of the fusion protein, selection of stably transfected cell clones or cell pools expressing the fusion protein, development of a Master Cell Bank for production of the fusion protein, purification of the fusion protein by Protein A affinity chromatography and/or SEC, and formulation using methods well described in the art.

Example 2
Anti-PDL1-BTLAecd, Anti-PDL1-TGFbRII, Anti-PDL1-TGFbRIIecd-BTLAecd, Anti-PD1-BTLAecd, Anti-PD1-TGFbRIIecd, and Anti-PD1-TGFbRIIecd-BTLAecd Fusion Proteins

Anti-PDL1-BTLAecd was designed to target both PD-L1 and BTLA ligand (HVEM) by fusing the C-terminus of the heavy chain of an anti-PDL1 antibody with a ligand binding sequence of the extracellular domain of human BTLA (BTLAecd) via a flexible linker peptide, (GGGGS)3. Anti-PDL1-TGFbRIIecd-BTLAecd was designed to target PD-L1, TGFb, and BLTA ligands (HVEM) by fusing the C-terminus of the heavy chain of an anti-PDL1 antibody with a ligand binding sequence of the extracellular domain of human TGFbRII (TGFbRIIecd) via a flexible linker peptide, (GGGGS)3, and fusing the C-terminus of the light chain of an anti-PDL1 antibody with a ligand binding sequence of the extracellular domain of human BTLA (BTLAecd) via a flexible linker peptide, (GGGGS)3.

Anti-PD1-BTLAecd was designed to target both PD-1 and BTLA ligand (HVEM) by fusing the C-terminus of the heavy chain of an anti-PD1 antibody (pembrolizumab) with a ligand binding sequence of the extracellular domain of human BTLA (BTLAecd) via a flexible linker peptide, (GGGGS)3. Anti-PD1-TGFbRIIecd was designed to target PD-1 and TGFb by fusing the C-terminus of the heavy chain of an anti-PD1 antibody (pembrolizumab) with a ligand binding sequence of the extracellular domain of human TGFbRII (TGFbRIIecd) via a flexible linker peptide, (GGGGS)3. Anti-PD1-TGFbRIIecd-BTLAecd was designed to target PD-1, TGFb, and BTLA ligands (HVEM) by fusing the C-terminus of the heavy chain of an anti-PD1 antibody (pembrolizumab) with a ligand binding sequence of the extracellular domain of human TGFbRII (TGFbRIIecd) via a flexible linker peptide, (GGGGS)3, and fusing the C-terminus of the light chain of an anti-PD1 antibody with a ligand binding sequence of the extracellular domain of human BTLA (BTLAecd) via a flexible linker peptide, (GGGGS)3.

FIG. 3 shows the characterization of anti-PDL1-BTLAecd, anti-PDL1-TGFbRII and anti-PDL1-TGFbRIIecd-BTLAecd. SDS-PAGE under reducing (R) and non-reducing (NR) conditions was used to compare the full-length (FL), heavy chain (HC) and light chain (LC) of anti-PDL1 (atezolizumab), anti-PDL1-BTLAecd and anti-PDL1-TGFbRIIecd-BTLAecd (FIG. 3A). SDS-PAGE confirmed the expected higher molecular weight of the heavy chain of anti-PDL1-BTLAecd compared to the heavy chain of anti-PDL1 antibody. SDS-PAGE of anti-PDL1-BTLAecd confirmed the expected higher molecular weight of the heavy chain compared to the heavy chain of anti-PDL1 antibody (Light chain of anti-PDL1-BTLAecd is identical to anti-PDL1). SDS-PAGE of anti-PDL1-TGFbRIIecd-BTLAecd confirmed the expected higher molecular weight of the heavy chain (anti-PDL1 HC fused to TGFbRIIecd) compared to the heavy chain of anti-PDL1 antibody, and the expected higher molecular weight of the light chain (anti-PDL1 LC fused to BTLAecd) compared to the light chain of anti-PDL1.

SEC-HPLC analysis of anti-PDL1 (atezolizumab), anti-PDL1-BTLAecd and anti-PDL1-TGFbRIIecd-BTLAecd (>99% monomericity) (FIG. 3B).

FIG. 4 shows the target binding ability of anti-PDL1-BTLAecd, anti-PDL1-TGFbRII and anti-PDL1-TGFbRIIecd-BTLAecd. Standard ELISA showing the ability of anti-PDL1 (atezolizumab), anti-PDL1-BTLAecd and anti-PDL1-TGFbRIIecd-BTLAecd to bind PD-L1. Plate was coated with the indicated amount of each antibody or ALT (0-1 ug/mL) followed by addition of biotinylated huPD-L1 (1 ug/ml) (FIG. 4A). Binding to biotinylated PD-L1 was detected by avidin-HRP (ELISA). Plate coated with anti-PD1 (nivolumab) served as a negative control (FIG. 4A).

Standard ELISA showing the ability of anti-PDL1-TGFbRIIecd and anti-PDL1-TGFbRIIecd-BTLAecd to bind TGFb. Plate was coated with the indicated amount of anti-PDL1-TGFbRIIecd, anti-PDL1-TGFbRIIecd-BTLAecd, anti-PDL1-BTLAecd, or TGFbRIIecd-Fc (0-1 ug/mL) followed by addition of biotinylated TGFb (1 ng/ml) (FIG. 4B). Binding to biotinylated TGFb was detected by avidin-HRP (ELISA). Plate coated with TGFbRIIecd-Fc served as a positive control, and plate coated with anti-PDL1-BTLAecd served as a negative control (FIG. 4B).

Standard ELISA showing the ability of anti-PDL1-BTLAecd and anti-PDL1-TGFbRIIecd-BTLAecd to bind the BTLA ligand HVEM. Plate was coated with 5 ug/mL of each antibody-ligand trap (anti-PDL1-BTLAecd and anti-PDL1-TGFbRIIecd-BTLAecd) followed by addition of varying amounts of biotinylated huHVEM (0-1 ug/ml). Binding to biotinylated HuHVEM was detected by avidin-HRP (ELISA) (FIG. 4C).

ELISA showing the ability of anti-PDL1-BTLAecd and anti-PDL1-TGFbRIIecd-BTLAecd to simultaneously bind PD-L1 and the BTLA ligand HVEM (FIG. 4D). Varying amounts of each antibody (0-2 ug/mL; anti-PDL1-BTLAecd or anti-PDL1-TGFbRIIecd-BTLAecd) were added to plate coated with 1 ug/mL PDL1-Fc, and then washed before addition of 500 ng/mL biotinylated huHVEM. The ability of PD-L1-bound anti-PDL1-BTLAecd or anti-PDL1-TGFbRIIecd-BTLAecd to simultaneously bind biotinylated huHVEM (via BTLAecd fused to the heavy or light chain respectively) was detected by avidin-HRP (ELISA).

The ability of anti-PDL1, anti-PDL1-BTLAecd to elicit antitumor immunity and inhibit the growth of syngeneic B16-F10 tumors in C57BL/6 muMt-mice is shown in FIG. 5A. B16-F10 murine melanoma tumor cells were subcutaneously inoculated in B cell-deficient C57BL/6 muMt- (B cell deficient) mice (1×105 tumor cells/mouse). Mice bearing tumor xenografts were randomized into groups (n=5 per group) and treated with vehicle alone (control) or each of the following antibodies (5 mg/kg i.p/week): anti-PDL1 (atezolizumab) or anti-PDL1-BTLAecd. Treatment with anti-PDL1-BTLAecd was significantly more effective in inhibiting tumor growth compared to anti-PD-L1 (atezolizumab).

The ability of anti-PDL1, anti-PDL1-BTLAecd to elicit antitumor immunity and inhibit the growth of cancers was examined in human immune reconstituted NSG mice bearing human WiDR-colorectal cancer cells is shown in FIG. 5B. NSG mice immune were reconstituted with tumor-matched HLA A2+ human CD34+ HSC followed by subcutaneous implantation of WiDR tumor xenografts (3×106 tumor cells in Matrigel). Humanized mice bearing tumor xenografts were randomized into groups (n=6 per group) and treated with vehicle alone (control) or each of the following antibodies (5 mg/kg i.p q 6d): anti-PDL1 (atezolizumab), anti-PDL1-BTLAecd. Treatment with anti-PDL1-BTLAecd was significantly more effective in inhibiting tumor growth compared to anti-PD-L1 (atezolizumab)(p<0.02).

The ability of anti-PDL1, anti-PDL1-BTLAecd, anti-PDL1-TGFbRIIecd and anti-PDL1-BTLAecd-TGFbRIIecd to elicit antitumor immunity and inhibit the growth of cancers was examined in human immune reconstituted NSG mice bearing human BXPC3-pancreatic cancer cells. NSG mice immune were reconstituted with tumor-matched HLA A2+ human CD34+ HSC followed by subcutaneous implantation of BXPC3 tumor xenografts (3×106 tumor cells in Matrigel) is shown in FIG. 5C. Humanized mice bearing tumor xenografts were randomized into groups (n=6 per group) and treated with vehicle alone (control) or each of the following antibodies (5 mg/kg i.p q 6d): anti-PDL1 (atezolizumab), anti-PDL1-BTLAecd, anti-PDL1-TGFbRIIecd and anti-PDL1-BTLAecd-TGFbRIIecd. Treatment with anti-PDL1-BTLAecd-TGFbRIIecd was significantly more effective in inhibiting tumor growth compared to anti-PD-L1 (atezolizumab)(p<0.001), anti-PDL1-BTLAecd, or anti-PDL1-TGFbRIIecd (p<0.05).

These data demonstrate that BTLA ECD fused to the heavy or light chain of an antibody is capable of binding HVEM, thereby disrupting native BTLA-mediated SHP1/SHP2 inhibition and promoting HVEM-mediated co-stimulatory signaling. Furthermore, these data demonstrate that inhibition of BTLA/HVEM signaling with a decoy BTLA receptor ECD fused to a polypeptide that binds and disables another immuno-inhibitory molecule is effective in the treatment of cancer. Furthermore, these data demonstrate that the decoy BTLA receptor ECD fused to a polypeptide that binds and disables another T cell co-inhibitory molecule is effective in the treatment of cancer. Furthermore, these data demonstrate that decoy BTLA receptor ECD fused to a polypeptide that inhibits the interaction of a cytokine and its cytokine receptor is effective in the treatment of cancer. Furthermore, these data demonstrate that decoy BTLA receptor ECD fused to a polypeptide that binds a tumor cell surface molecule is effective in the treatment of cancer. Furthermore, these data demonstrate that decoy BTLA receptor ECD on either the heavy or light chain of the targeting polypeptide is capable of binding HVEM, thereby disrupting native BTLA-mediated SHP1/SHP2 inhibition and promoting HVEM-mediated co-stimulatory signaling, even while another receptor ECD is additionally fused to the antibody. Furthermore, these data demonstrate that decoy BTLA receptor ECD is effective in the treatment of cancer when part of a fusion protein comprising an additional ECD of a cytokine or cytokine receptor. Furthermore, these data demonstrate that decoy BTLA receptor ECD fused to an antibody can enable recruitment of T cells to tumor cells, since these data show that BTLA ECD can bind HVEM while the targeting antibody simultaneously binds a T cell surface molecule.

Example 3
Anti-VEGF-PD1 Fusion Protein

Mice are treated with mAbs 24 h prior to the radiotracer injection. Tissues are collected at 60 min after radiotracer injection, weighed and counted for radioactivity. Data is normalized for tissue weight and injected dose and presented as % ID/g. The radiotracer comprises a labeled high-affinity PDL1-binding peptide. Low % ID/g indicates effective competition with the labeled PD-L1 binding peptide. anti-VEGF-PD1 competes as effectively as anti-PDL1 mAb for binding PD-L1 in the tumor (FIG. 6A). CD3+ are counted in immunohistochemistry images of tumors in control group. anti-VEGF group, or anti-VEGF-PD1 ECD group. Treatment with anti-VEGF-PD1 results in significant increase of CD3+ cells (FIG. 6B). NSG mice immune reconstituted with tumor-matched HLA A2+ human CD34+ HSC and bearing KRAS mutant D-MUT1 human colorectal cancer tumor xenografts were treated (5 mg/kg i.p. weekly) with vehicle alone (untreated control) or the following antibodies (either alone or in combination), as indicated: with either vehicle alone (untreated control) or the following antibodies: anti-VEGF-PD1ecd; anti-VEGF (bevacizumab) [>=5 mice/group] (FIG. 6C). Tumor size was measured blinded to the treatment group and tumor volume was calculated using the formula (length×width×height). In vivo tumor growth curves (mean+SEM) are shown. p values were derived using unpaired, two-sided t-test.

These data demonstrate that a fusion protein that blocks VEGF and also comprises the ECD of a molecule that inhibits immune cells (e.g., T cells, dendritic cells, macrophages) is effective in treating cancer. These data demonstrate that a fusion protein that blocks VEGF and also comprises the ECD of a T cell co-inhibitory molecule is effective in treating cancer. These data demonstrate that a fusion protein that blocks VEGF and also comprises a polypeptide that binds a tumor cell surface molecule or molecule enriched in the tumor microenvironment is effective in localizing VEGF to the tumor microenvironment.

Example 4
Anti-VEGF-TGFbRII-PD1 Fusion Protein

Structure of anti-VEGF-TGFbRII-PD1 (FIG. 7A). anti-VEGF binds VEGF, TGFbRII binds TGFb, PD1 binds PD-L1 and PD-L2. NSG mice immune were reconstituted with tumor-matched HLA A2+ human CD34+ HSC followed by subcutaneous implantation of WiDR tumor xenografts (1.5×106 tumor cells in Matrigel) (FIG. 7B). Humanized mice bearing tumor xenografts were randomized into groups (n=5 per group) and treated with vehicle alone (control) or equimolar doses of each of the following antibodies (i.p q6d): anti-VEGF, anti-VEGF-PD1, anti-VEGF-TGFbRII-PD1. Treatment with anti-VEGF-TGFbRII-PD1 was significantly more effective in inhibiting tumor growth compared to anti-VEGF-PD1 or anti-VEGF. NSG mice immune were reconstituted with tumor-matched HLA A2+ human CD34+ HSC followed by subcutaneous implantation of BXPC3 tumor xenografts (2×106 tumor cells in Matrigel) (FIG. 7C). Humanized mice bearing tumor xenografts were randomized into groups (n=5 per group) and treated with vehicle alone (control) or equimolar doses of each of the following antibodies (i.p q6d): anti-VEGF, anti-VEGF+anti-PDL1, anti-VEGF-TGFbRII-PD1. Treatment with anti-VEGF-TGFbRII-PD1 was significantly more effective in inhibiting tumor growth compared to anti-VEGF+anti-PDL1 or anti-VEGF.

Standard ELISA showing the ability of anti-VEGF (bevacizumab), anti-VEGF-TGFbRII-PD1 to bind VEGF (FIG. 8A). Plate was coated with 2 ug/mL of anti-VEGF-PD1-TGFbRII or anti-VEGF (bevacizumab), followed by addition of biotinylated huVEGF in the amount indicated. Binding to biotinylated VEGF was detected by avidin-HRP (ELISA).

Standard ELISA showing the ability of anti-VEGF-TGFbRII-PD1 to bind TGFb (FIG. 8B). Plate was coated with the indicated amount of anti-VEGF-TGFbRII-PD1 (0-10 ug/mL) followed by addition of biotinylated PD-L1 (1000 ng/ml) or biotinylated PD-L1 (400 ng/mL). Binding to biotinylated PD-L1/PD-L2 was detected by avidin-HRP (ELISA).

Standard ELISA showing the ability of anti-VEGF-TGFbRII-PD1 to bind TGFb as well as IgG-TGFbRII (FIG. 8C). Plate was coated with 1 ug/mL of anti-VEGF-TGFbRII-PD1, IgG-TGFbRII as positive control, or anti-VEGF (bevacizumab) as negative control, followed by addition of varying amounts of biotinylated huTGFb1 (0-2000 pg/ml). Binding to biotinylated huTGFb1 was detected by avidin-HRP (ELISA)

These data demonstrate that blockade of TGFb and VEGF is more effective in treatment of cancer than blockade of VEGF alone. These data further demonstrate that a fusion protein comprising an anti-VEGF/VEGFR polypeptide and another polypeptide that inhibits angiogenesis (e.g., TGFb) is effective in the treatment of cancer. These data further demonstrate that a fusion protein comprising an antibody that inhibits angiogenesis fused to a receptor ECD that inhibits angiogenesis is effective in the treatment of cancer.

These data further demonstrate that a fusion protein comprising anti-VEGF/VEGFR antibody and a receptor ECD that inhibits angiogenesis is effective in the treatment of cancer. These data further demonstrate that a fusion protein comprising an anti-angiogenic polypeptide and a polypeptide that inhibits a key determinant of TH17 differentiation is effective in the treatment of cancer. These data further demonstrate that localized blockade of VEGF and/or TGFb in the tumor microenvironment is effective in the treatment of cancer.

Example 5
Anti-HER2-TGFbRII, Anti-HER2-PD1, Anti-EGFR-TGFbRII Fusion Proteins

SDS-PAGE under reducing (R) and non-reducing (NR) conditions was used to compare the full-length (FL), heavy chain (HC) and light chain (LC) of anti-HER2-TGFβRIIecd, anti-HER2-PD1ecd, and anti-HER2 (Trastuzumab) (FIG. 9A). The assay was repeated after storage of anti-HER2-TGFbRIIecd for 12 months at 4° C. to ensure its stability (right-most two lanes; marked in red).

The ability of anti-HER2-TGFβRII to simultaneously bind HER2 and TGF-β1 was evaluated by a ‘double-sandwich’ ELISA wherein anti-HER2-TGFβRIIecd was added to HER2-Fc coated plates, followed by rhTGF-β1 (1 ng/ml) that was detected by a biotinylated anti-huTGF-β1 antibody (FIG. 9B). The plate was incubated with Avidin-HRP and developed with TMB substrate. anti-HER2-TGFβRIIecd exhibited simultaneous binding to HER2 and TGF-β1.

The ability of anti-HER2-TGFβRII to bind TGF-β1 was also evaluated by competition immunoassays (FIG. 9C). The ELISA plate was coated with capture antibody (anti-TGF-β Ab, 1 μg/ml), followed by rhTGF-β1 in the presence of either anti-HER2-TGFβRII or anti-HER2 mAb (TGF-β1: antibody ratio, 1:1 to 1:100) for 1 h at RT. Unlike anti-HER2 mAb, anti-HER2-TGFβRII antibody exhibited the ability to compete for binding to TGF-β1.

The HER2-overexpressing human breast cancer cell line BT-474 was cultured in vitro in the presence of escalating concentrations of anti-HER2 mAb (trastuzumab: 5 μg/ml-20 μg/ml) for 3 months. Trastuzumab-resistant cells that continued to grow in the presence of trastuzumab (20 μg/ml) for 30 days were isolated and implanted subcutaneously into the R flank of 4-6 week female BALB/c nude mice bearing estrogen pellets (8×10⁶cells/mouse). At 21d following tumor cell inoculation, the mice were randomized and treated with anti-HER2 mAb (Trastuzumab) (5 mg/kg, i.p, weekly×6 wks). anti-HER2 mAb failed to stop tumor progression.

To evaluate the antitumor activity of anti-HER2-TGFβRIIecd against tumors that resisted anti-HER2 mAb in vivo (TrastuzumabR BT-474), trastuzumab-resistant tumors harvested from trastuzumab-treated F1 mice were sectioned into 2×2 mm pieces and implanted subcutaneously into a second cohort of female BALB/c nude mice (TrastuzumabR BT-474-F2). Tumor-bearing F2 mice were treated with either trastuzumab (5 mg/kg, i.p, every 2 weeks×6) or anti-HER2-TGFβRIIecd (5 mg/kg i.p. every 2 weeks×6).

Residual tumors in TrastuzumabR BT-474 (BT-474-TR) F2 tumor-bearing mice following treatment with anti-HER2-TGFβRII were significantly smaller (mean±SEM=31.7±6.5) than those in F2 mice treated with anti-HER2 mAb (mean±SEM=453.9±121.4)(p=0.003) (FIG. 10A).

Whereas treatment of F2 mice bearing TrastuzumabR BT-474 tumor xenografts with trastuzumab showed continued tumor progression in 4/6 mice, all 7 mice treated with anti-HER2-TGFβRII showed complete inhibition of tumor growth (p=0.009).

Serum was collected from TrastuzumabR BT-474 tumor-bearing mice. A hydrochloric acid pre-treatment was performed, and serum concentrations of TGF-β1 were measured by ELISA (FIG. 10B).

In vivo treatment of tumor-bearing mice with anti-HER2-TGFbRIIecd completely sequestered activated serum TGFβ1 7 days after treatment.

Human tumor xenografts were generated by mammary fat pad implantation of the MDA-MB-231-Luc (D3H2LN) TNBC line in female immune deficient NOG mice (NOD/Shi-scid IL-2rgnull) (FIG. 11A). NOG mice (6-8 week old) were irradiated at 200 cGy and rested for 6-8 h, followed by adoptive transfer of human CD34+ cells (7×104/mouse) from a normal donor (HLA-matched to the TNBC line) (ALLCELLS). Mice were tested for engraftment of human CD3+ T cells in peripheral blood obtained via tail-bleed at 6-7 weeks following injection of CD34+ cells. The cells were stained with anti-huCD3-PE and anti-huCD19-FITC, and analyzed by flow cytometry. Mice demonstrating human CD3+ cell engraftment were injected with MDA-MB-231-Luc cells (2×106 cells in 50% PBS/50% matrigel). At 7d following tumor cell inoculation, mice were randomized and treated for 4 weeks with the following: (i) anti-EGFR-TGFβRII (5 mg/kg i.p. weekly); (ii) anti-EGFR mAb (Cetuximab; 5 mg/kg, i.p, weekly); (iii) anti-TGFβ Ab (1D11; 5 mg/kg i.p. weekly); (iv) Vehicle (Control). Treatment with anti-EGFR-TGFβRII resulted in significantly smaller tumors (257.6±58.5) compared to tumors in mice treated with cetuximab (766.3±64) (p<0.0001) or untreated controls (839.4±77.4)(p<0.0001).

Immune deficient NSG mice (NOD/Shi-scid IL-2rgnull; 6-8 weeks old) were irradiated at 200 cGy and rested for 6-8 h, followed by adoptive transfer of human CD34+ cells (7×104/mouse) from a normal donor (HLA-matched to the D-MUT1 line)(ALLCELLS) (FIG. 11B). Mice were tested for engraftment of human CD3+ T cells in peripheral blood obtained via tail-bleed at 8 weeks following injection of CD34+ cells. The cells were stained with anti-huCD3-PE, and analyzed by flow cytometry. Mice demonstrating human CD3+ cell engraftment were inoculated subcutaneously with a PDX of human HNSCC (moderately-poorly differentiated SCC harvested from the vocal cord). At 18 days following tumor cell inoculation, mice were randomized and treated with the following: (i) anti-EGFR-TGFβRIIecd (5 mg/kg i.p. weekly); (ii) anti-EGFR mAb (Cetuximab; 5 mg/kg, i.p, weekly); (iii) Vehicle (Untreated Control). Treatment with anti-EGFR-TGFβRIIecd resulted in significantly smaller tumors (261.3.1±95.0) compared to tumors in mice treated with cetuximab (588.6.0±61.9) (p=0.03) or untreated controls (898.0±85.4) (p=0.002).

Nude mice were inoculated subcutaneously with a PDX of human HNSCC (SCC harvested from the floor of the mouth) (FIG. 11C). At 21 days following tumor cell inoculation, mice were randomized and treated with the following: (i) anti-EGFR-TGFβRIIecd (5 mg/kg i.p. weekly); (ii) anti-EGFR mAb (Cetuximab; 5 mg/kg, i.p, weekly); (iii) Vehicle (Untreated Control). Treatment with anti-EGFR-TGFβRIIecd resulted in significantly smaller tumors (131.1±29.3) compared to tumors in mice treated with cetuximab (918.4±311.2) (p<0.05) or untreated controls (1107.9±210.0) (p=0.002).

These data demonstrate that tumor-targeted TGFbRII is effective in treating cancer. These data further demonstrate that fusion proteins comprising TGFbRII and a polypeptide that induces or promotes ADCC/FcR-mediated cross-presentation is effective in treating cancer.

Example 6
Anti-PD1-TIM3 and Anti-PDL1-TIM3 Fusion Proteins

Schematic of anti-PD1-TIM3ecd and anti-PDL1-TIM3ecd (FIG. 12A). Anti-PDL1-TIM3ecd was designed to target both PD-L1 and TIM3 ligands by fusing the C-terminus of the heavy chain of an anti-PDL1 antibody with a ligand binding sequence of the extracellular domain of TIM3 (TIM3ecd) via a flexible linker peptide, (GGGGS)3. Anti-PD1-TIM3ecd was designed to target both PD-1 and TIM3 ligands by fusing the C-terminus of the heavy chain of an anti-PD1 antibody with a ligand binding sequence of the extracellular domain of TIM3 (TIM3ecd) via a flexible linker peptide, (GGGGS)3.

The ability of anti-PD1-TIM3ecd and anti-PDL1-TIM3ecd to elicit antitumor immunity and inhibit the growth of cancers that are refractory to current checkpoint inhibitors, such as triple-negative breast cancer (TNBC) was investigated. Approximately 15-25% of patients with breast cancer have TNBC, an aggressive type that does not respond to hormonal agents or targeted therapy and has an increased risk of metastases. We used human immune reconstituted NSG mice bearing the bioluminescent human MDA-MB-231-luc (D3H2LN) TNBC cell line that expresses elevated PD-L1.

Anti-PD1-TIM3ecd (430.3±29.9) inhibits tumor growth significantly more effectively than untreated control (908.2±40.3), anti-PD-1 (824.0±38.3), IgG-TIM3ecd (825.1±79.0) or the combination of IgG-TIM3ecd and anti-PD1 (884.7±97.4) (p<0.0001) (FIG. 12B).

NSG mice immune reconstituted with tumor-matched HLA A2+ human CD34+ HSC and bearing MDA-MB23 1-Luc human TNBC tumor xenografts were treated (5 mg/kg i.p. every 6 days) with vehicle alone (untreated control) or the following antibodies (either alone or in combination), as indicated: with either vehicle alone (untreated control) or the following antibodies: anti-PD1-TIM3ecd; anti-PD1 (nivolumab); anti-TIM-3 (F38-2E2); or combination of anti-PD1 and anti-TIM-3.

Anti-PDL1-TIM3ecd (226.4±71.4) inhibits tumor growth more effectively than anti-PDL1 (617.5±144.3), anti-TIM-3 (640.9±99.6) or the combination of anti-TIM-3 and anti-PDL1 mAbs (653.0±59.8) (p<0.001) (FIG. 12B).

Treatment of MDA-MB-231-luc-bearing mice with either anti-PDL1, anti-PD1, anti-TIM3, or the combination of anti-PDL1 and anti-TIM-3 mAbs failed to inhibit tumor growth compared to untreated animals. In contrast, treatment with anti-PDL1-TIM3ecd was significantly more effective at inhibiting the progression of MDA-MB-231-luc tumors compared with untreated controls, or animals treated with either anti-PDL1, anti-PD1, anti-TIM3, or the combination of anti-PDL1 and anti-TIM-3 mAbs. NSG mice immune reconstituted with tumor-matched HLA A2+ human CD34+ HSC and bearing MDA-MB231-Luc human TNBC tumor xenografts were treated (5 mg/kg i.p. every 6 days) with vehicle alone (untreated control) or the following antibodies (either alone or in combination), as indicated: with either vehicle alone (untreated control) or the following antibodies: anti-PDL1-TIM3ecd; anti-PDL1 (atezolizumab); anti-TIM-3; anti-PD-1 (pembrolizumab); combination of anti-PDL1 and anti-TIM-3.

Although the invention has been described with reference to the above examples, it will be understood that modifications and variations are encompassed within the spirit and scope of the invention. Accordingly, the invention is limited only by the following claims.

MOLECULES, COMPOSITIONS AND METHODS FOR TREATMENT OF CANCER

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