Pd-1 antibodies in combination with a cytokine-secreting cell and methods of use thereof

Abstract

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.

What is claimed is: 
     
         1 . A method of cancer immunotherapy comprising: administering a combination of a cytokine-expressing cellular immunotherapy and an antibody that specifically binds to human Programmed Death 1 (anti-PD-1) to a subject with cancer, wherein administration of the combination results in enhanced therapeutic efficacy relative to administration of the cytokine-expressing cellular immunotherapy or the anti-PD-1 antibody alone. 
     
     
         2 . The method of  claim 1 , wherein the cytokine-expressing cellular immunotherapy expresses GM-CSF. 
     
     
         3 . The method of  claim 1 , wherein the combination comprises cells that are autologous to the subject. 
     
     
         4 . The method of  claim 1 , wherein the combination comprises cells that are allogeneic to the subject. 
     
     
         5 . The method of  claim 1 , wherein the combination comprises bystander cells. 
     
     
         6 . The method of  claim 1 , wherein the cytokine-expressing cellular immunotherapy is rendered proliferation-incompetent by irradiation. 
     
     
         7 . The method of  claim 1 , wherein the subject is a human. 
     
     
         8 . The method of  claim 1 , wherein the cancer is a prostate cancer. 
     
     
         9 . The method of  claim 1 , wherein the cancer is a non-small cell lung carcinoma. 
     
     
         10 . The method of  claim 1 , wherein the cancer is a melanoma. 
     
     
         11 . The method of  claim 1 , wherein the cancer is a colorectal cancer. 
     
     
         12 . The method of  claim 1 , wherein the cancer is a renal cell carcinoma. 
     
     
         13 . The method of  claim 1 , wherein the cancer is an ovarian cancer. 
     
     
         14 . The method of  claim 4 , 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. 
     
     
         15 . The method of  claim 9 , wherein the cytokine-expressing cellular immunotherapy is rendered proliferation-incompetent by irradiation. 
     
     
         16 . The method of  claim 1 , wherein the anti-PD-1 antibody is monoclonal. 
     
     
         17 . The method of  claim 1 , wherein the anti-PD-1 antibody is mammalian. 
     
     
         18 . The method of  claim 1 , wherein the anti-PD-1 antibody is fully human. 
     
     
         19 . The method of  claim 1 , wherein the anti-PD-1 antibody is humanized. 
     
     
         20 . The method of  claim 1 , wherein the cytokine-expressing cellular immunotherapy is administered subcutaneously. 
     
     
         21 . The method of  claim 1 , wherein the cytokine-expressing cellular immunotherapy is administered intratumorally. 
     
     
         22 . The method of  claim 1 , wherein the cytokine-expressing cellular immunotherapy is intradermally. 
     
     
         23 . The method of  claim 1 , wherein the anti-PD-1 antibody is administered subcutaneously. 
     
     
         24 . The method of  claim 1 , wherein the anti-PD-1 antibody is administered intratumorally. 
     
     
         25 . The method of  claim 1 , wherein the anti-PD-1 antibody is administered intradermally. 
     
     
         26 . The method of  claim 1 , wherein the anti-PD-1 antibody is administered intravenously. 
     
     
         27 . The method of  claim 1 , wherein the anti-PD-1 antibody is administered simultaneously with administration of the GM-CSF-expressing cellular immunotherapy. 
     
     
         28 . The method of  claim 1 , wherein the anti-PD-1 antibody is administered one, two, three, four, five, six, seven, or more days after administration of the GM-CSF-expressing cellular immunotherapy. 
     
     
         29 . The method of  claim 1 , wherein the GM-CSF-expressing cellular immunotherapy is administered one, two, three, four, five, six, seven, or more days after administration of the anti-PD-1 antibody. 
     
     
         30 . The method of  claim 1 , wherein the anti-PD-1 antibody is administered simultaneously with administration of the GM-CSF-expressing cellular immunotherapy on a biweekly basis. 
     
     
         31 . The method of  claim 1 , wherein enhanced therapeutic efficacy is measured by increased overall survival time. 
     
     
         32 . The method of  claim 1 , wherein enhanced therapeutic efficacy is measured by increased progression-free survival. 
     
     
         33 . The method of  claim 1 , wherein enhanced therapeutic efficacy is measured by decreased tumor size. 
     
     
         34 . A composition for cancer therapy comprising: a cytokine-expressing cellular immunotherapy and an antibody that specifically binds to human Programmed Death 1 (anti-PD-1), 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. 
     
     
         35 . The composition of  claim 34 , wherein the cells of said cytokine-expressing cellular immunotherapy are autologous to the subject. 
     
     
         36 . The composition of  claim 34 , wherein the cells of said cytokine-expressing cellular immunotherapy are allogeneic to the subject. 
     
     
         37 . The composition of  claim 34 , wherein the cells of said cytokine-expressing cellular immunotherapy cells are bystander cells. 
     
     
         38 . The composition of  claim 34 , wherein the cells of said cytokine-expressing cellular immunotherapy are rendered proliferation-incompetent by irradiation. 
     
     
         39 . The composition of  claim 36 , 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. 
     
     
         40 . The composition of  claim 34 , wherein the anti-PD-1 antibody is monoclonal. 
     
     
         41 . The composition of  claim 34 , wherein the anti-PD-1 antibody is mammalian. 
     
     
         42 . The composition of  claim 34 , wherein the anti-PD-1 antibody is fully human. 
     
     
         43 . The composition of  claim 34 , wherein the anti-PD-1 antibody is humanized. 
     
     
         44 . The composition of  claim 34 , wherein enhanced therapeutic efficacy is measured by increased overall survival time. 
     
     
         45 . The composition of  claim 34 , wherein enhanced therapeutic efficacy is measured by increased progression-free survival. 
     
     
         46 . The composition of  claim 34 , wherein enhanced therapeutic efficacy is measured by decreased tumor size. 
     
     
         47 . The composition of  claim 34 , wherein the cytokine-expressing cellular immunotherapy expresses GM-CSF. 
     
     
         48 . A kit comprising:
 a first composition comprising a cytokine-expressing cellular immunotherapy and a second composition comprising an antibody that specifically binds to human Programmed Death 1 (PD-1), wherein administration of the first and second compositions to a subject with cancer results in enhanced therapeutic efficacy relative to administration of the cytokine-expressing cellular immunotherapy or the antibody that specifically binds to PD-1 alone.   
     
     
         49 . The kit of  claim 48 , further comprising instructions directing administration of the first and second compositions. 
     
     
         50 . The kit of  claim 48 , wherein said instructions direct simultaneous administration of the first and second compositions. 
     
     
         51 . The kit of  claim 48 , wherein said instructions direct administration of the first and second compositions simultaneously. 
     
     
         52 . The kit of  claim 48 , wherein said instructions further direct administration of the first and second compositions simultaneously on a biweekly basis. 
     
     
         53 . The kit of  claim 48 , wherein said instructions direct administration of the second composition one, two, three, four, five, six, seven, or more days subsequent to administration of the first composition. 
     
     
         54 . The kit of  claim 48 , wherein said instructions direct administration of the first composition one, two, three, four, five, six, seven, or more days subsequent to administration of the second composition. 
     
     
         55 . The kit of  claim 48 , wherein the cytokine-expressing cellular immunotherapy expresses GM-CSF.