Cancer immunotherapy compositions and methods of use

Abstract

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.

We claim: 
     
         1 . A cellular composition for generating an immune response to cancer in a human subject, comprising: a melanoma antigen and one or more populations of cells genetically modified to express the coding sequence for IL-12 and the coding sequence of an anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody. 
     
     
         2 . The composition according to  claim 1 , wherein said melanoma antigen is expressed by a cell. 
     
     
         3 . The composition according to  claim 1 , wherein the same population of cells is genetically modified to express the coding sequence for IL-12 and an anti-CTLA4 antibody. 
     
     
         4 . The composition according to  claim 1 , wherein two different populations of cells are genetically modified to express the coding sequence for IL-12 and an anti-CTLA4 antibody. 
     
     
         5 . The composition according to  claim 1 , wherein at least one of said one or more populations of genetically modified cells are tumor cells. 
     
     
         6 . (canceled) 
     
     
         7 . The composition according to  claim 6 , wherein said anti-CTLA4 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-CTLA4 antibody, a proteolytic cleavage site, a sequence encoding a self-processing cleavage site and the coding sequence for the second chain of an anti-CTLA4 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-CTLA4 antibody. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . The composition according to  claim 3 , wherein said cells are autologous. 
     
     
         12 . The composition according to  claim 3 , wherein said cells are allogeneic. 
     
     
         13 . The composition according to  claim 3 , wherein said cells are bystander cells. 
     
     
         14 . The composition according to  claim 5 , wherein said cells are autologous. 
     
     
         15 . The composition according to  claim 5 , wherein said cells are allogeneic. 
     
     
         16 . The composition according to  claim 5 , wherein said cells are bystander cells. 
     
     
         17 . The composition according to  claim 6 , wherein said tumor antigen-expressing population of cells are autologous. 
     
     
         18 . The composition according to  claim 6 , wherein said tumor antigen-expressing population of cells are allogeneic. 
     
     
         19 . The composition according to  claim 6 , wherein said tumor antigen-expressing population of cells are bystander cells. 
     
     
         20 . The composition according to  claim 8 , wherein said tumor antigen-expressing population of cells are autologous. 
     
     
         21 . The composition according to  claim 8 , wherein said-tumor antigen-expressing population of cells are allogeneic. 
     
     
         22 . The composition according to  claim 8 , wherein said tumor antigen-expressing population of cells are bystander cells. 
     
     
         23 . The composition according to  claim 9 , wherein said tumor antigen-expressing population of cells are autologous. 
     
     
         24 . The composition according to  claim 9 , wherein said tumor antigen-expressing population of cells are allogeneic. 
     
     
         25 . The composition according to  claim 9 , wherein said tumor antigen-expressing population of cells are bystander cells. 
     
     
         26 . The composition according to  claim 4 , wherein one of said different populations of genetically modified cells are autologous. 
     
     
         27 . The composition according to  claim 4 , wherein at least one of said different populations of genetically modified cells are allogeneic. 
     
     
         28 . The composition according to  claim 4 , wherein at least one of said different populations of genetically modified cells are bystander cells. 
     
     
         29 - 38 . (canceled) 
     
     
         39 . A method for cancer therapy and generating an immune response to cancer to a human subject, comprising:
 administering a cellular composition to a human subject, said composition comprising: a melanoma antigen and one or more populations of cells genetically modified to express the coding sequence for IL-12 and the coding sequence of an anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody, wherein administration of the combination to the subject results in enhanced therapeutic efficacy relative to administration of a melanoma antigen and a population of cells genetically modified to express the coding sequence for IL-12 alone.   
     
     
         40 . The method according to  claim 39 , wherein said melanoma antigen is expressed by a cell. 
     
     
         41 . The method according to  claim 39 , wherein the same population of cells is genetically modified to express the coding sequence for a cytokine and an anti-CTLA4 antibody. 
     
     
         42 . The method according to  claim 39 , wherein two different populations of cells are genetically modified to express the coding sequence for IL-12 and an anti-CTLA4 antibody. 
     
     
         43 . The method according to  claim 39 , wherein at least one of said one or more populations of genetically modified cells are tumor cells. 
     
     
         44 . The method according to  claim 43 , wherein said tumor antigen-expressing population of cells is genetically modified to express the coding sequence for IL-12 and an anti-CTLA4 antibody. 
     
     
         45 . The method according to  claim 43 , wherein said tumor antigen-expressing population of cells is genetically modified to express the coding sequence for IL-12. 
     
     
         46 . The method according to  claim 43 , wherein said melanoma antigen-expressing population of cells is genetically modified to express the coding sequence for an anti-CTLA4 antibody. 
     
     
         47 . The method according to  claim 46 , wherein said anti-CTLA4 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-CTLA4 antibody, a proteolytic cleavage site, a sequence encoding a self-processing cleavage site and the coding sequence for the second chain of an anti-CTLA4 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-CTLA4 antibody. 
     
     
         48 . The method according to  claim 44 , wherein said cells are autologous. 
     
     
         49 . The method according to  claim 44 , wherein said cells are allogeneic. 
     
     
         50 . The method according to  claim 44 , wherein said cells are bystander cells. 
     
     
         51 . The method according to  claim 45 , wherein said cells are autologous. 
     
     
         52 . The method according to  claim 45 , wherein said cells are allogeneic. 
     
     
         53 . The method according to  claim 45 , wherein said cells are bystander cells. 
     
     
         54 . The method according to  claim 46 , wherein said cells are autologous. 
     
     
         55 . The method according to  claim 46 , wherein said cells are allogeneic. 
     
     
         56 . The method according to  claim 46 , wherein said cells are bystander cells.