Claims
- 1. A method for transferring a protein to a cell comprising: coating the surface of said cell with a first protein, wherein said first protein is a lipidated protein; and
contacting said cell with a second protein, wherein said second protein is a fusion protein having a first domain having affinity for said lipidated protein and a second domain capable of binding to a receptor on said cell's surface.
- 2. The method of claim 1 wherein said cell is a T cell.
- 3. The method of claim 2 wherein said T cell is a CD4-positive T cell.
- 4. The method of claim 2 wherein said T cell is a CD8-positive T cell.
- 5. The method of claim 2 wherein said T cell is a tumor-infiltrating lymphocyte.
- 6. The method of claim 2 wherein said T cell has specificity for a tumor antigen.
- 7. The method of claim 2 wherein said T cell has specificity for a viral peptide antigen.
- 8. The method of claim 1 wherein said cell is selected from the group consisting of a lymphokine-activated killer cell, a dendritic cell, a monocyte, a B cell, a natural killer cell, a neutrophil, an eosinophil, a basophil, a mast cell, a keratinocyte, an endothelial cell, an islet cell, a fibroblast, an osteoblast, a chondrocyte, a muscle cell, and a neural cell.
- 9. The method of claim 1 wherein said cell is a stem cell.
- 10. The method of claim 9 wherein said stem cell is selected from the group consisting of a hematopoietic stem cell, a mesenchymal stem cell, and an embryonic stem cell.
- 11. The method of claim 1 wherein said second domain of said fusion protein comprises a costimulator domain that has the ability to activate said cell.
- 12. The method of claim 11 wherein said costimulator domain is selected from the group consisting of B7-1, B7-2, ICAM-1, ICAM-2, ICAM-3, CD48, LFA-3, CD30 ligand, CD40 ligand, heat stable antigen, B7 h, 4-1BB ligand, OX40 ligand, LIGHT, CD70 and CD24.
- 13. The method of claim 1 wherein said second domain of said fusion protein comprises a major histocompatibility complex protein complexed with a peptide antigen.
- 14. The method of claim 1 wherein said second domain of said fusion protein has the ability to activate a cell selected from the group consisting of an antigen-presenting cell, a B cell, a natural killer cell, a neutrophil, an eosinophil, a basophil, a mast cell, a stem cell, a keratinocyte, an endothelial cell, an islet cell, a fibroblast, an osteoblast, a chondrocyte, a muscle cell, and a neural cell.
- 15. The method of claim 14 wherein said second domain of said fusion protein comprises a domain selected from the group consisting of CD40 ligand, TRANCE, Flt-3 ligand, GM-CSF, VEGF, and FGF.
- 16. The method of claim 1 wherein said second domain of said fusion protein comprises an inhibitor domain that has the ability to inhibit said cell.
- 17. The method of claim 16 wherein said cell is a stem cell.
- 18. The method of claim 16 wherein said inhibitor domain has the ability to inhibit or induce apoptosis in a T cell.
- 19. The method of claim 18 wherein said inhibitor domain is selected from the group consisting of Fas ligand and TRAIL and said cell is a T cell.
- 20. The method of claim 1 wherein said second domain of said fusion protein comprises a poly-histidine tag.
- 21. The method of claim 1, wherein said fusion protein comprises a chimeric Fc fusion protein and said lipidated protein is palmitated-protein A.
- 22. The method of claim 1 wherein said lipidated protein is selected from the group consisting of palmitated-protein A and chelator lipid NTA-DTDA.
- 23. The method of claim 1, further comprising the step of purifying said cell prior to coating said surface.
- 24. The method of claim 1, wherein more than one second protein is transferred to said cell.
- 25. A method of treating a patient for an illness comprising:
coating the surface of a plurality of cells with a first protein, wherein said first protein is a lipidated protein; and contacting said plurality of cells with a second protein, wherein said second protein is a fusion protein comprised of a first domain having affinity for said first protein and a second domain capable of binding to a receptor on said cell's surface and specific for the treatment of the illness; and administering an effective amount of said coated cells to said patient.
- 26. The method of claim 25, wherein said illness is selected from the group consisting of cancer, viral infection, autoimmune disease and alloimmune disease.
- 27. The method of claim 25, wherein said cells are injected into said patient.
- 28. The method of claim 25, further comprising culturing said cells ex vivo prior to said adminstration to said patient.
- 29. The method of claim 25, wherein said cells are lymphokine-activated killer cells and said patient is a cancer patient.
- 30. The method of claim 25, wherein said cells are tumor infiltrating lymphocytes and said patient is a cancer patient.
- 31. The method of claim 25, wherein said coating step and said contacting step take place in vivo.
- 32. The method of claim 25, wherein said coating step and said contacting step take place in vitro.
- 33. Cells made by the method of claim 1.
- 34. The cells of claim 33, wherein said cells are T cells.
- 35. The cells of claim 34, wherein said T cells are CD4-positive T cells.
- 36. The cells of claim 34, wherein said T cells are CD8-positive T cells.
- 37. The cells of claim 34, wherein said T cells are tumor-infiltrating lymphocytes.
- 38. The cells of claim 34, wherein said T cells have specificity for a tumor antigen.
- 39. The cells of claim 34, wherein said T cells have specificity for a viral peptide antigen.
- 40. The cells of claim 33, wherein said cells are selected from the group consisting of lymphokine-activated killer cells, dendritic cells, monocytes, B cells, natural killer cells, neutrophils, eosinophils, basophils, mast cells, keratinocytes, endothelial cells, islet cells, fibroblasts, osteoblasts, chondrocytes, muscle cells, and neural cells.
- 41. The cells of claim 33, wherein said cells are stem cell.
- 42. The cells of claim 41 wherein said stem cells are selected from the group consisting of hematopoietic stem cells, mesenchymal stem cells, and embryonic stem cells.
- 43. The cells of claim 33 wherein said second domain of said fusion protein comprises a costimulator domain that has the ability to activate said cells.
- 44. The cells of claim 43 wherein said costimulator domain is selected from the group consisting of B7-1, B7-2, B7 h, ICAM-1, ICAM-2, ICAM-3, CD48, LFA-3, CD30 ligand, CD40 ligand, heat stable antigen, 4-1BB ligand, OX40 ligand, LIGHT, CD70 and CD24.
- 45. The cells of claim 33 wherein said second domain of said fusion protein comprises a major histocompatibility complex protein complexed with a peptide antigen.
- 46. The cells of claim 33 wherein said second domain of said fusion protein has the ability to activate a cell selected from the group consisting of an antigen-presenting cell, a B cell, a natural killer cell, a neutrophil, an eosinophil, a basophil, a mast cell, a stem cell, a keratinocyte, an endothelial cell, an islet cell, a fibroblast, an osteoblast, a chondrocyte, a muscle cell, and a neural cell.
- 47. The cells of claim 46 wherein said second domain of said fusion protein is selected from the group consisting of CD40 ligand, TRANCE, Flt-3 ligand, GM-CSF, VEGF, and FGF.
- 48. The cells of claim 33 wherein said second domain of said fusion protein comprises an inhibitor domain that has the ability to inhibit said cell.
- 49. The cells of claim 33 wherein said cells are stem cells.
- 50. The cells of claim 48 wherein said inhibitor domain has the ability to inhibit or induce apoptosis in a T cell.
- 51. The cells of claim 50 wherein said inhibitor domain is selected from the group consisting of Fas ligand and TRAIL and said cells are T cells.
- 52. The cells of claim 33 wherein said second domain of said fusion protein comprises a poly-histidine tag.
- 53. The cells of claim 33, wherein said fusion protein comprises a chimeric Fc fusion protein and said lipidated protein is palmitated-protein A.
- 54. The cells of claim 33 wherein said lipidated protein is selected from the group consisting of palmitated-protein A and chelator lipid NTA-DTDA.
- 55. The cells of claim 33, wherein said cells are purifed prior to coating said surface of said cells.
- 56. The cells of claim 33, wherein more than one second protein is transferred to said cell.
- 57. A pharmaceutical composition for treating a patient for an illness comprising cells made by the method of claim 1, in a suitable carrier.
- 58. The composition of claim 57, wherein said illness is selected from the group consisting of cancer, viral infection, autoimmune disease and alloimmune disease.
- 59 The composition of claim 58, wherein said cells are lymphokine-activated killer cells and said patient is a cancer patient.
- 60. The composition of claim 57, wherein said cells are tumor infiltrating lymphocytes and said patient is a cancer patient.
- 61. A method for transferring a protein to a cell comprising:
coating the surface of said cell with a fusion protein, said fusion protein comprising a first domain and a second domain; said first domain capable of becoming incorporated into a membrane of said cell, and said second domain capable of binding to a receptor on said cell's surface.
- 62. The method of claim 61 wherein said first domain comprises a glycophospholipid.
- 63. The method of claim 62, wherein said glycophospholipid is glycosyl phosphatidylinositol.
- 64. A method for transferring a protein to a cell of a patient comprising:
injecting into said patient a fusion protein, said fusion protein comprising a first domain and a second domain; said first domain comprising a homing element capable of attaching to said cell, and said second domain capable of binding to a receptor on said cell's surface.
- 65. The method of claim 64, wherein said homing element is a scFv.
- 66. The method of claim 64, wherein said homing element is a cytokine.
- 67. A cell comprising a cDNA sequence encoding a membrane protein having the capacity to bind a receptor on the surface of said cell.
- 68. A cell comprising a cDNA sequence encoding a membrane receptor with the capacity to bind a ligand on the surface of said cell.
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation-in-part of application Ser. No. 09/957,056, filed Sep. 20, 2001, which is a divisional application of 09/476,828, filed Jan. 3, 2000, now U.S. Pat. No. 6,316,256, expressly incorporated herein by reference.
Government Interests
[0002] This work was supported in part by Grants R01 CA-74958 and R01 AI-31044 from the National Institutes of Health.
Provisional Applications (1)
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Number |
Date |
Country |
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60398050 |
Jul 2002 |
US |
Divisions (1)
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Number |
Date |
Country |
Parent |
09476828 |
Jan 2000 |
US |
Child |
10205524 |
Jul 2002 |
US |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
09957056 |
Sep 2001 |
US |
Child |
10205524 |
Jul 2002 |
US |