PS-1 antibodies in combination with a cytokine-secreting cell and methods of use thereof
View Patent ↗The present invention relates to a method of enhancing the anti-tumor response in a mammal. More particularly, the invention is concerned with combinations comprising a cytokine-secreting cell and an anti-PD-1 antibody, and methods of administering the combination for enhanced immune response to tumor cells in a patient with a cancer.
1. A method of cancer immunotherapy comprising:
administering a cytokine-expressing cellular immunotherapy comprising cells modified to express GM-CSF and a single chain antibody that specifically binds to human Programmed Death 1 (anti-PD-1) to a subject with cancer,
wherein the modified cells are rendered proliferation-incompetent by irradiation, and
wherein administration of the cells modified to express GM-CSF and the single chain antibody results in enhanced therapeutic efficacy relative to administration of an anti-PD-1 antibody alone or cells modified to express GM-CSF alone.
2. The method of claim 1 , wherein the cytokine-expressing cellular immunotherapy comprises cells that are autologous to the subject.
3. The method of claim 1 , wherein the cytokine-expressing cellular immunotherapy comprises cells that are allogeneic to the subject.
4. The method of claim 3 , wherein the allogeneic cells are a tumor cell line selected from the group consisting of a prostate tumor line, a non-small cell lung carcinoma line and a pancreatic cancer line.
5. The method of claim 1 , wherein the cytokine-expressing cellular immunotherapy comprises bystander cells.
6. The method of claim 1 , wherein the subject is a human.
7. The method of claim 1 , wherein the cancer is a prostate cancer.
8. The method of claim 1 , wherein the cancer is a non-small cell lung carcinoma.
9. The method of claim 1 , wherein the cancer is a melanoma.
10. The method of claim 1 , wherein the cancer is a colorectal cancer.
11. The method of claim 1 , wherein the cancer is a renal cell carcinoma.
12. The method of claim 1 , wherein the cancer is an ovarian cancer.
13. The method of claim 1 , wherein the cytokine-expressing cellular immunotherapy is administered subcutaneously.
14. The method of claim 1 , wherein the cytokine-expressing cellular immunotherapy is administered intratumorally.
15. The method of claim 1 , wherein the cytokine-expressing cellular immunotherapy is intradermally.
16. The method of claim 1 , wherein the cytokine-expressing cellular immunotherapy is administered intravenously.
17. The method of claim 1 , wherein enhanced therapeutic efficacy is measured by increased overall survival time.
18. The method of claim 1 , wherein enhanced therapeutic efficacy is measured by increased progression-free survival.
19. The method of claim 1 , wherein enhanced therapeutic efficacy is measured by decreased tumor size.