Cytokine-expressing cellular vaccine combinations
The present invention in all of its associated aspects provides improved methods and compositions for treating cancer in a mammal based on the administration of the combination of a cytokine-expressing cellular vaccine and at least one additional cancer therapeutic agent or treatment to a patient with cancer, wherein administration of the combination results in enhanced therapeutic efficacy relative to administration of the cytokine-expressing cellular vaccine or cancer therapeutic agent or treatment as a monotherapy.
1 . An improved method for cancer therapy, comprising:
administering the combination of a cytokine-expressing cellular vaccine and at least one additional cancer therapeutic agent selected from the group consisting of an anti-CTLA4 antibody, an anti-4-1BB antibody, interferon-alpha, docetaxel, paclitaxel, a COX-2 inhibitor, an anti-CD40 antibody or CD40 ligand, an anti-OX40 antibody or OX-40 ligand and a heat shock protein (HSP), to a subject with cancer, wherein administration of the combination to the subject results in enhanced therapeutic efficacy relative to administration of the cytokine-expressing cellular vaccine or the at least one additional cancer therapeutic agent alone.
2 . The method of claim 1 , wherein the cytokine-expressing cellular vaccine expresses GM-CSF.
3 . The method of claim 2 , wherein the cells of said cytokine-expressing cellular vaccine are autologous to the subject.
4 . The method of claim 2 , wherein the cells of said cytokine-expressing cellular vaccine are allogeneic to the subject.
5 . The method of claim 2 , wherein the cells of said cytokine-expressing cellular vaccine cells are bystander cells.
6 . The method of claim 2 , wherein the cells of the cytokine-expressing cellular vaccine are rendered proliferation-incompetent by irradiation.
7 . The method of claim 2 , wherein the mammal is a human.
8 . The method of claim 2 , wherein the cancer is a prostate cancer.
9 . The method of claim 2 , wherein the cancer is a non-small cell lung carcinoma.
10 . 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.
11 . The method of claim 2 , wherein said at least one additional cancer therapeutic agent includes an anti-CTLA4 antibody.
12 . The method of claim 2 , wherein said at least one additional cancer therapeutic includes an anti-4-1BB antibody.
13 . The method of claim 2 , wherein said at least one additional cancer therapeutic agent includes interferon-alpha.
14 . The method of claim 2 , wherein said at least one additional cancer therapeutic agent includes docetaxel or paclitaxel.
15 . The method of claim 14 , wherein said at least one additional cancer therapeutic agent includes docetaxel.
16 . The method of claim 2 , wherein said at least one additional cancer therapeutic agent includes a COX-2 inhibitor.
17 . The method of claim 16 , wherein said COX-2 inhibitor is Celecoxib.
18 . The method of claim 2 , wherein said at least one additional cancer therapeutic agent includes an anti-CD40 antibody or CD40 ligand.
19 . The method of claim 2 , wherein said at least one additional cancer therapeutic agent is expressed by a cell and the cell is an autologous, allogeneic or a bystander cell.
20 . The method of claim 19 , wherein the autologous, allogeneic or a bystander cell is rendered proliferation-incompetent by irradiation.
21 . The method of claim 20 , wherein the autologous, allogeneic or a bystander cell expresses interferon-alpha.
22 . The method of claim 20 , wherein the autologous, allogeneic or a bystander cell expresses CD40 ligand.
23 . The method of claim 2 , wherein said cytokine-expressing cellular vaccine is administered subcutaneously.
24 . The method of claim 2 , wherein said cytokine-expressing cellular vaccine is administered intratumorally.
25 . The method of claim 16 , wherein said COX-2 inhibitor is administered before the GM-CSF-expressing cellular vaccine.
26 . The method of claim 18 , wherein said anti-CD40 antibody is administered after the GM-CSF-expressing cellular vaccine.
27 . The method of claim 18 , wherein said CD40 ligand is administered after the GM-CSF-expressing cellular vaccine.
28 . An improved composition for cancer therapy, comprising:
a GM-CSF expressing cellular vaccine and at least one additional cancer therapeutic agent selected from the group consisting of an anti-CTLA4 antibody, an anti-4-188 antibody, interferon-alpha, docetaxel, Celecoxib, an anti-CD40 antibody and CD40 ligand for administration to a subject with cancer, wherein administration of the combination results in enhanced therapeutic efficacy relative to administration of the GM-CSF expressing cellular vaccine or the at least one additional cancer therapeutic agent alone.
29 . The composition of claim 28 , wherein the cells of said cytokine-expressing cellular vaccine are autologous to the subject.
30 . The composition of claim 28 , wherein the cells of said cytokine-expressing cellular vaccine are allogeneic to the subject.
31 . The composition of claim 28 , wherein the cells of said cytokine-expressing cellular vaccine cells are bystander cells.
32 . The composition of claim 28 , wherein the cells of said cytokine-expressing cellular vaccine are rendered proliferation-incompetent by irradiation.
33 . The composition of claim 30 , 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.
34 . The composition of claim 28 , wherein said at least one additional cancer therapeutic agent is an anti-CTLA4 antibody.
35 . The composition of claim 28 , wherein said at least one additional cancer therapeutic is an anti-4-1BB antibody.
36 . The composition of claim 28 , wherein said at least one additional cancer therapeutic agent is interferon-alpha.
37 . The composition of claim 28 , wherein said at least one additional cancer therapeutic agent is docetaxel.
38 . The composition of claim 28 , wherein said at least one additional cancer therapeutic agent is Celecoxib.
39 . The composition of claim 28 , wherein said at least one additional cancer therapeutic agent is an anti-CD40 antibody or CD40 ligand.
40 . The composition of claim 28 , wherein said at least one additional cancer therapeutic agent is expressed by a cell and the cell is autologous, allogeneic or a bystander cell.
41 . The composition of claim 40 , wherein the autologous, allogeneic or bystander cell is rendered proliferation-incompetent by irradiation.
42 . The composition of claim 41 , wherein the autologous, allogeneic or a bystander cell expresses interferon-alpha.
43 . The composition of claim 41 , wherein the he autologous, allogeneic or a bystander cell expresses CD40 ligand.