PD-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 composition for cancer therapy comprising:
a cytokine-expressing cellular immunotherapy comprising cells modified to express a cytokine and a single chain antibody that specifically binds to human Program Death 1 (anti-PD-1), wherein the cells of said cytokine-expressing cellular immunotherapy are rendered proliferation-incompetent by irradiation,
wherein administration of the composition to a subject with cancer results in enhanced therapeutic efficacy relative to administration of the cytokine-expressing cellular immunotherapy or the anti-PD-1 antibody alone.
2. The composition of claim 1 , wherein the cells of said cytokine-expressing cellular immunotherapy are autologous to the subject.
3. The composition of claim 1 , wherein the cells of said cytokine-expressing cellular immunotherapy are allogeneic to the subject.
4. The composition of claim 3 , wherein said 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 composition of claim 1 , wherein the cells of said cytokine-expressing cellular immunotherapy cells are bystander cells.
6. The composition of claim 1 , wherein the anti-PD-1 antibody is mammalian.
7. The composition of claim 1 , wherein the anti-PD-1 antibody is fully human.
8. The composition of claim 1 , wherein the anti-PD-1 antibody is humanized.
9. The composition of claim 1 , wherein enhanced therapeutic efficacy is measured by increased overall survival time.
10. The composition of claim 1 , wherein enhanced therapeutic efficacy is measured by increased progression-free survival.
11. The composition of claim 1 , wherein enhanced therapeutic efficacy is measured by decreased tumor size.
12. The composition of claim 1 , wherein the cytokine-expressing cellular immunotherapy expresses GM-CSF.
13. The composition of claim 1 , wherein the cells comprise a single population of cells in which each cell of the population expresses both a cytokine and an anti-PD-1 antibody.
14. A kit comprising the composition of claim 1 .
15. The kit of claim 14 , further comprising instructions directing administration of the composition.
16. The kit of claim 15 , wherein said instructions further direct administration of the composition on a biweekly basis.
17. The kit of claim 14 , wherein the cytokine-expressing cellular immunotherapy expresses GM-CSF.
18. The kit of claim 14 , wherein the cells comprise a single population of cells in which each cell of the population expresses both a cytokine and an anti-PD-1 antibody.