CANCER IMMUNOTHERAPY COMPOSITIONS AND METHODS OF USE
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 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.