Claims
- 1. A method for eliciting an immune response to an antigen in a subject comprising
(a) administering at least one antigen-presenting cell (APC) chemotaxin and an antigen.
- 2. A method of enhancing an immune response of a subject to an antigen comprising administering an APC chemotaxin and the antigen.
- 3. The method of claim 2, wherein the immune response is an antibody-mediated immune response.
- 4. The method of claim 3, wherein the administering increases the titer of antigen-specific antibodies by greater than at least 2-fold.
- 5. The method of claim 2, wherein the immune response is a cell-mediated immune response.
- 6. The method of claim 2, wherein the APC chemotaxin is chemotactic for a dendritic cell.
- 7. The method of claim 2, wherein the APC chemotaxin is chemotactic for an immature dendritic cell.
- 8. The method of claim 2, wherein the APC chemotaxin and antigen are co-administered.
- 9. The method of claim 2, wherein the APC chemotaxin and antigen are administered separately.
- 10. The method of claim 2, comprising administering at least two APC chemotaxins.
- 11. The method of claim 2, wherein the APC chemotaxin is a chemokine polypeptide or a variant thereof.
- 12. The method of claim 2, wherein the APC chemotaxin is a chimeric polypeptide comprising a sequence of at least 10 contiguous residues from a chemokine polypeptide and a sequence of at least 10 contiguous residues from a second chemokine polypeptide.
- 13. The method of claim 11, wherein the chemokine polypeptide is selected from the group consisting of hMIP1α, hMIP1α (70aa), mMIP-1α, hRANTES, hMET-RANTES, mRANTES, hHCC-1, hMPIF-1, hMPIF-1 (22-137), hMPIF-1 (46-137), hMIP-1δ, hMCP-4, mMCP-5, mMARC, mEotaxin, mMCP-1 (JE), mTECK, mMIP-2, mBLC, hLeukotactin, mMIG, mMIP-1β. hMCP-2, hMCP-3, vMIP-1, hMIP-3α, hMIP-3β, mC10, mMDC, hMIP-1, vMCK-2, and mMIP-1γ.
- 14. The method of claim 11, wherein the chemokine polypeptide is selected from the group consisting of mC10, mMDC, hMIP-1 βand mMIP-1γ.
- 15. The method of claim 11, wherein the chemokine polypeptide is mC10.
- 16. The method of claim 11, wherein the chemokine polypeptide is VMCK-2.
- 17. The method of claim 11, wherein the chemokine polypeptide is selected from the group consisting of hMCP-2, hMCP-3, vMIP-1, hMIP-3 αvMCK-2 and hMIP-3β.
- 18. The method of claim 11, wherein at least one of the first or second chemokine polypeptide is selected from the group consisting of hMIP1α, hMIP1α (70aa), mMIP-1α, hRANTES, hMET-RANTES, mRANTES, hHCC-1, hMPIF-1, hMPIF-1 (22-137), hMPIF-1 (46-137), hMIP-1δ, hMCP-4, mMCP-5, mMARC, mEotaxin, mMCP-1 (JE), mTECK, mMIP-2, mBLC, hLeukotactin, mMIG, mMIP-1β. hMCP-2, hMCP-3, vMIP-1, hMIP-3α, hMIP-3β, mC10, mMDC, hMIP-1β, vMCK-2, and mMIP-1γ.
- 19. The method of claim 2, wherein t he APC chemotaxin is formulated in a sustained release pharmaceutical com position.
- 20. The method of claim 2, wherein the antigen is a polypeptide from a pathogen.
- 21. The method of claim 20, wherein the pathogen is Hepatitis or Influenza.
- 22. The method of claim 2, wherein the antigen is a tumor antigen.
- 23. The method of claim 2, further comprising administering an adjuvant.
- 24. The method of claim 23, wherein the adjuvant is selected from the group consisting of alum, incomplete Freund's adjuvant, a bacterial capsular polysaccharide, dextran, IL-12, GM-CSF, CD40 ligand, IFN-gamma, IL-1, IL-2, IL-3, IL-4, IL-10, IL-13, IL-18, and a cytokine.
- 25. The method of claim 2, further comprising a multivalent carrier.
- 26. The method of claim 25, wherein the multivalent carrier is linked to the APC chemotaxin, the antigen or an adjuvant.
- 27. The method of claim 25, wherein the multivalent carrier is selected from the group consisting of a bacterial capsular polysaccharide, a dextran and a genetically engineered vector.
- 28. The method of claim 27, wherein the bacterial capsular polysaccharide is from Pneumococci, Streptococci, or Meningococci.
- 29. The method of claim 2, further comprising administering a pharmaceutical carrier.
- 30. The method of claim 2, wherein the administering is into a solid tumor.
- 31. The method of claim 2, wherein the administering is into the tissue surrounding a solid tumor.
- 32. The method of claim 2, wherein the administering is injecting.
- 33. The method of claim 2, wherein the administering is inhaling.
- 34. The method of claim 2, wherein the administering an APC chemotaxin comprises administering a polynucleotide encoding the APC chemotaxin.
- 35. The method of claim 2, wherein the administering an antigen comprises administering a polynucleotide encoding the antigen.
- 36. The method of claim 2, wherein the subject is a human.
- 37. A composition comprising
(a) at least one APC chemotaxin, and (b) at least one antigen.
- 38. The composition of claim 37, wherein the APC chemotaxin is substantially purified.
- 39. The composition of claim 37, wherein the APC chemotaxin is chemotactic for dendritic cells.
- 40. The composition of claim 39, wherein the APC chemotaxin is chemotactic for immature dendritic cells.
- 41. The composition of claim 37, wherein the APC chemotaxin is not chemotactic for at least one cell selected from the group consisting of neutrophil, T cell, B cell, monocyte and eosinophil.
- 42. The composition of claim 37, comprising at least two APC chemotaxins.
- 43. The composition of claim 37, wherein the APC chemotaxin is a chemokine polypeptide or a variant thereof.
- 44. The composition of claim 37, wherein the APC chemotaxin is a chemokine polypeptide.
- 45. The composition of claim 44, wherein the APC chemotaxin is a naturally occurring chemokine polypeptide.
- 46. The composition of claim 37, wherein the APC chemotaxin is in a sustained release formulation.
- 47. The composition of claim 37, further comprising at least one pharmaceutically acceptable carrier.
- 48. The composition of claim 47, wherein the pharmaceutically acceptable carrier is an adjuvant.
- 49. The composition of claim 47, wherein the pharmaceutically acceptable carrier is selected from the group consisting of water, an oil, a saline solution, aqueous dextrose and glycerol solution.
- 50. An immunogenic composition comprising a cell exogenously expressing an APC chemotaxin.
- 51. The immunogenic composition of claim 50, wherein the cell is allogeneic.
- 52. The immunogenic composition of claim 50, wherein the cell is autologous.
- 53. The immunogenic composition of claim 50, further comprising a tumor-associated antigen.
- 54. The immunogenic composition of claim 50, wherein the cell is a cancer cell.
- 55. The immunogenic composition of claim 54, wherein the cancer cell is from a cancer cell line.
- 56. The immunogenic composition of claim 55, wherein the cancer cell line is a human ovarian cancer cell line or a human brain cancer cell line.
- 57. The immunogenic composition of claim 50, further comprising a tumor-associated antigen.
- 58. The immunogenic composition of claim 57, wherein the tumor-associated antigen is obtained from an autologous cell of a subject.
- 59. An immunogenic composition, comprising:
(a) at least one tumor cell, and (b) at least one cell exogenously expressing an APC chemotaxin.
- 60. The immunogenic composition of claim 59, wherein the tumor cell is a primary tumor cell.
- 61. The immunogenic composition of claim 59, wherein the tumor cell is autologous to a subject to whom the immunogenic composition is intended.
- 62. The immunogenic composition of claim 59, wherein the tumor cell is a glioma, glioblastoma, gliosarcoma, astrocytoma, melanoma, breast cancer cell or an ovarian cancer cell.
- 63. The immunogenic composition of claim 59, wherein the tumor cell is quiescent.
- 64. The immunogenic composition of claim 59, wherein the tumor cell is a cancer cell.
- 65. The immunogenic composition of claim 59, wherein the cell exogenously expressing an APC chemotaxin is allogenic.
- 66. The immunogenic composition of claim 59, wherein the cell exogenously expressing an APC chemotaxin is quiescent.
- 67. A method of formulating a composition capable of eliciting an immune response to an antigen in a subject comprising:
(a) isolating a polypeptide having an activity of an APC chemotaxin, and (b) combining the polypeptide with the antigen.
- 68. A kit comprising:
(a) a pharmaceutical composition comprising an APC chemotaxin and a pharmaceutically acceptable carrier, and (b) a syringe.
RELATED APPLICATIONS
[0001] This application claims priority to U.S. nonprovisional application Ser. No. 09/834,814, filed Apr. 20, 2001, which is incorporated herein by reference in its entirety.