Constitutive expression of costimulatory ligands on adoptively transferred T lymphocytes
The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing at least one of an antigen-recognizing receptor and a co-stimulatory ligand and methods of use therefore for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.
1. A method of treating a neoplasia in a subject in need thereof, the method comprising administering to the subject an effective amount of a T cell comprising (1) two exogenous co-stimulatory ligands that are 4-1BBL and CD80, and (2) a receptor that binds an antigen.
2. The method of claim 1 , wherein the method increases an immune response.
3. The method of claim 1 , wherein the neoplasia is selected from the group consisting of prostate cancer, colon cancer, breast cancer, and glioblastoma.
4. The method of claim 1 , wherein the T cell is collected from an autologous or allogeneic donor, or generated in vitro from an engineered progenitor or stem cell.
5. The method of claim 1 , wherein the receptor is constitutively expressed on the surface of the T cell.
6. The method of claim 1 , wherein the two co-stimulatory ligands are constitutively or inducibly expressed on the surface of the T cell.
7. The method of claim 1 , wherein the antigen is a tumor antigen.
8. The method of claim 7 , wherein the antigen is selected from the group consisting of prostate-specific membrane antigen (PSMA), Carcinoembryonic Antigen (CEA), IL13Ralpha, her-2, CD19, NY-ESO-1, Lewis Y, Mart-1, gp100, tyrosinase, WT-1, hTERT, and mesothelin.
9. The method of claim 1 , wherein the receptor that binds the antigen comprises a recombinant antigen receptor.
10. The method of claim 1 , wherein the two co-stimulatory ligands are expressed from a retroviral vector.
11. The method of claim 1 , wherein the T cell is a cytotoxic T lymphocyte (CTL).
12. The method of claim 9 , wherein the recombinant antigen receptor is a chimeric antigen receptor.
13. The method of claim 12 , wherein the chimeric antigen receptor is Pz1.
14. The method of claim 12 , wherein the chimeric antigen receptor is P28z.
15. The method of claim 1 , wherein the receptor that binds the antigen comprises an endogenous antigen receptor.
16. A method of treating a neoplasia in a subject in need thereof, the method comprising administering to the subject an effective amount of a T cell comprising (1) two exogenous co-stimulatory ligands that are 4-1 BBL and CD86, and (2) a receptor that binds an antigen.
17. The method of claim 16 , wherein the method increases an immune response.
18. The method of claim 16 , wherein the neoplasia is selected from the group consisting of prostate cancer, colon cancer, breast cancer, and glioblastoma.
19. The method of claim 16 , wherein the T cell is collected from an autologous or allogeneic donor, or generated in vitro from an engineered progenitor or stem cell.
20. The method of claim 16 , wherein the receptor is constitutively expressed on the surface of the T cell.
21. The method of claim 16 , wherein the two co-stimulatory ligands are constitutively or inducibly expressed on the surface of the T cell.
22. The method of claim 16 , wherein the two co-stimulatory ligands are expressed from a retroviral vector.
23. The method of claim 16 , wherein the antigen is a tumor antigen.
24. The method of claim 23 , wherein the antigen is selected from the group consisting of prostate-specific membrane antigen (PSMA), Carcinoembryonic Antigen (CEA), IL13Ralpha, her-2, CD19, NY-ESO-1, Lewis Y, Mart-1, gp100, tyrosinase, WT-1, hTERT, and mesothelin.
25. The method of claim 16 , wherein the receptor that binds the antigen comprises a recombinant antigen receptor.
26. The method of claim 25 , wherein the recombinant antigen receptor is a chimeric antigen receptor.
27. The method of claim 26 , wherein the chimeric antigen receptor is Pz1.
28. The method of claim 26 , wherein the chimeric antigen receptor is P28z.
29. The method of claim 16 , wherein the receptor that binds the antigen comprises an endogenous antigen receptor.
30. The method of claim 16 , wherein the T cell is a cytotoxic T lymphocyte (CTL).