Cancer immunotherapy compositions and methods of use
View Patent ↗Cellular compositions and methods for inducing an immune response to tumor cells are described. The cellular compositions include a tumor antigen and cells that have been modified to express a cytokine and one or more of a tumor antigen, anti-CTLA4 antibody and an additional cytokine. The cellular compositions find utility in methods for treating cancer.
1. A cellular composition for generating an immune response to cancer in a human subject, comprising: a tumor antigen and one or more populations of cells genetically modified to express the coding sequence for a granulocyte-macrophage colony stimulating factor (GM-CSF) polypeptide and the coding sequence of an anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody, wherein the same population of cells is genetically modified to express the coding sequence for the GM-CSF polypeptide and the anti-CTLA-4 antibody.
2. The composition according to claim 1 , wherein said tumor antigen is expressed by a cell.
3. The composition according to claim 1 , wherein said genetically modified population of cells are tumor cells.
4. The composition according to claim 3 , wherein said genetically modified population of tumor cells expresses said tumor antigen.
5. The composition according to claim 1 , 3 or 4 , wherein said anti-CTLA-4 antibody is expressed using a vector comprising:
in the 5′ to 3′ direction, a promoter operably linked to the coding sequence for the first chain of an anti-CTLA-4 antibody, a proteolytic cleavage site, a sequence encoding a self-processing cleavage site and the coding sequence for the second chain of an anti-CTLA-4 antibody, wherein the sequence encoding the self-processing cleavage site is inserted between the coding sequence for the first chain and the second chain of said anti-CTLA-4 antibody.
6. The composition according to claim 1 , wherein said cells are autologous.
7. The composition according to claim 1 , wherein said cells are allogeneic.
8. The composition according to claim 1 , wherein said cells are bystander cells.
9. The composition according to claim 3 , wherein said cells are autologous.
10. The composition according to claim 3 , wherein said cells are allogeneic.
11. The composition according to claim 3 , wherein said cells are bystander cells.
12. The composition according to claim 4 , wherein said tumor antigen-expressing population of cells are autologous.
13. The composition according to claim 4 , wherein said tumor antigen-expressing population of cells are allogeneic.
14. The composition according to claim 4 , wherein said tumor antigen-expressing population of cells are bystander cells.
15. An improved method for cancer therapy
and generating an immune response to cancer to a human subject, by administering a cellular composition to a human subject, said composition comprising:
a tumor antigen and one or more populations of cells genetically modified to
express the coding sequence for a GM-CSF polypeptide and the coding sequence of an anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody, wherein the same population of cells is genetically modified to express the coding sequence for the GM-CSF polypeptide and the anti-CTLA-4 antibody, and wherein administration of the composition to the subject results in an enhanced therapeutic efficacy relative to administration of a tumor antigen and a population of cells genetically modified to express the coding sequence for a GM-CSF polypeptide alone.
16. The method according to claim 15 , wherein said tumor antigen is expressed by a cell.
17. The method according to claim 15 ,
wherein said one or more populations of cells genetically modified to express the coding sequence for a GM-CSF polypeptide and the coding sequence of an anti-cytotoxic T lymphocyte-associated antigen-4 antibody are tumor cells.
18. The method according to claim 17 , wherein said genetically modified population of tumor cells expresses said tumor antigen.
19. The method according to claim 15 , wherein said anti-CTLA-4 antibody is expressed using a vector comprising:
in the 5′ to 3′ direction, a promoter operably linked to the coding sequence for the first chain of an anti-CTLA-4 antibody, a proteolytic cleavage site, a sequence encoding a self-processing cleavage site and the coding sequence for the second chain of an anti-CTLA-4 antibody, wherein the sequence encoding the self-processing cleavage site is inserted between the coding sequence for the first chain and the second chain of said anti-CTLA-4 antibody.
20. The method according to claim 15 , wherein said cells genetically modified to express the coding sequence for a GM-CSF polypeptide and the coding sequence of an anti-cytotoxic T lymphocyte-associated antigen-4 antibody are autologous.
21. The method according to claim 15 , wherein said cells genetically modified to express the coding sequence for a GM-CSF polypeptide and the coding sequence of an anti-cytotoxic T lymphocyte-associated antigen-4 antibody are allogeneic.
22. The method according to claim 15 , wherein said cells genetically modified to express the coding sequence for a GM-CSF polypeptide and the coding sequence of an anti-cytotoxic T lymphocyte-associated antigen-4 antibody are bystander cells.
23. The method according to claim 17 , wherein said cells genetically modified to express the coding sequence for a GM-CSF polypeptide and the coding sequence of an anti-cytotoxic T lymphocyte-associated antigen-4 antibody are autologous.
24. The method according to claim 17 , wherein said cells genetically modified to express the coding sequence for a GM-CSF polypeptide and the coding sequence of an anti-cytotoxic T lymphocyte-associated antigen-4 antibody are allogeneic.
25. The method according to claim 17 , wherein said cells genetically modified to express the coding sequence for a GM-CSF polypeptide and the coding sequence of an anti-cytotoxic T lymphocyte-associated antigen-4 antibody are bystander cells.
26. The method according to claim 18 , wherein said cells genetically modified to express the coding sequence for a GM-CSF polypeptide and the coding sequence of an anti-cytotoxic T lymphocyte-associated antigen-4 antibody are autologous.
27. The method according to claim 18 , wherein said cells genetically modified to express the coding sequence for a GM-CSF polypeptide and the coding sequence of an anti-cytotoxic T lymphocyte-associated antigen-4 antibody are allogeneic.
28. The method according to claim 18 , wherein said cells genetically modified to express the coding sequence for a GM-CSF polypeptide and the coding sequence of an anti-cytotoxic T lymphocyte-associated antigen-4 antibody are bystander cells.