METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER
Provided herein are vaccine compositions having potent adjuvant activity. Such compositions are capable of increasing anti-gen-specific antibody responses and increased frequency of Her-2-specific CD4+ T-cells, have improved anti-tumor efficacy, and are useful in methods of treating cancer.
1 . A composition comprising a recombinant modified vaccinia virus Ankara (“MVA”) expressing a polypeptide comprising a heterologous tumor-associated antigen and a recombinant protein comprising the heterologous tumor-associated antigen.
2 . The composition of claim 1 , wherein the heterologous tumor-associated antigen comprises an antigen selected from the group consisting of a c-erbB-1 (“EGFr”) antigen, a c-erbB-2 (“HER-2” or “c-Neu”) antigen, a c-erbB-3 antigen and a c-erbB-4 antigen.
3 . The composition of claim 2 , wherein the heterologous tumor-associated antigen comprises a HER-2 antigen.
4 . The composition of claim 3 , wherein the HER-2 antigen comprises SEQ ID NO:1.
5 . The composition of claim 4 , wherein the MVA is MVA-Bavarian Nordic (“MVA-BN”).
6 . The composition of claim 5 , wherein administration of the composition induces an improved antigen-specific CD4+ T-cell response as measured by ELISPOT assay or increased antigen-specific antibody titers as measured by ELISA, compared to administration of a composition comprising only a recombinant MVA expressing a polypeptide comprising a heterologous tumor-associated antigen.
7 . The composition of claim 6 , further comprising one or more pharmaceutically acceptable diluents, buffers, excipients, or carriers.
8 . A method of treating a human cancer patient comprising: (a) identifying a human cancer patient having a cancer expressing a tumor-associated antigen; (b) administering to the patient a therapeutically effective amount of a recombinant modified vaccinia virus Ankara (“MVA”) expressing a polypeptide comprising the heterologous tumor-associated antigen and a therapeutically effective amount of a recombinant protein comprising the heterologous tumor-associated antigen, thereby treating the cancer.
9 . The method of claim 8 , wherein the heterologous tumor-associated antigen comprises an antigen selected from the group consisting of a c-erbB-1 (“EGFr”) antigen, a c-erbB-2 (“HER-2” or “c-Neu”) antigen, a c-erbB-3 antigen and a c-erbB-4 antigen.
10 . The method of claim 9 , wherein the heterologous tumor-associated antigen comprises a HER-2 antigen.
11 . The method of claim 10 , wherein the HER-2 antigen comprises SEQ ID NO:1.
12 . The method of claim 11 , wherein the MVA is MVA-BN.
13 . The method of claim 12 , wherein administration of the recombinant MVA and the recombinant protein together induces an improved antigen-specific CD4+ T-cell response as measured by ELISPOT assay or increased antigen-specific antibody titers as measured by ELISA, compared to administration of a composition comprising only a recombinant MVA expressing a polypeptide comprising a heterologous tumor-associated antigen.
14 . The method of claim 13 , wherein the recombinant MVA and the recombinant protein are formulated with one or more pharmaceutically acceptable diluents, buffers, excipients, or carriers.
15 . The method of claim 14 , wherein the human cancer patient has a HER-2 over-expressing cancer.
16 . The method of claim 15 , wherein the HER-2 over-expressing cancer is selected from the group consisting of breast cancer, colon cancer, lung cancer, gastric cancer, pancreatic cancer, bladder cancer, cervical cancer and ovarian cancer.
17 . The method of claim 16 , wherein the HER-2 over-expressing cancer is breast cancer.
18 . The method of claim 17 , wherein the breast cancer is metastatic breast cancer.
19 . A kit for treating a human cancer patient, comprising: (a) a recombinant modified vaccinia virus Ankara (“MVA”) expressing a polypeptide comprising a heterologous tumor-associated antigen; (b) a recombinant protein comprising the heterologous tumor-associated antigen; and (c) instructions to administer a therapeutically effective amount of the recombinant MVA and a therapeutically effective amount of the recombinant protein to a human cancer patient having a cancer expressing the heterologous tumor-associated antigen.
20 . The kit of claim 19 , wherein the heterologous tumor-associated antigen comprises an antigen selected from the group consisting of a c-erbB-1 (“EGFr”) antigen, a c-erbB-2 (“HER-2” or “c-Neu”) antigen, a c-erbB-3 antigen and a c-erbB-4 antigen.
21 . The kit of claim 20 , wherein the heterologous tumor-associated antigen comprises a HER-2 antigen.
22 . The kit of claim 21 , wherein the HER-2 antigen comprises SEQ ID NO:1.
23 . The kit of claim 22 , wherein the MVA is MVA-BN.
24 . The kit of claim 23 , wherein administration of the recombinant MVA and the recombinant protein together induces an improved antigen-specific CD4+ T-cell response as measured by ELISPOT assay or increased antigen-specific antibody titers as measured by ELISA, compared to administration of a composition comprising only a recombinant MVA expressing a polypeptide comprising a heterologous tumor-associated antigen.
25 . The kit of claim 24 , wherein the recombinant MVA and the recombinant protein are formulated with one or more pharmaceutically acceptable diluents, buffers, excipients, or carriers.
26 . The kit of claim 25 , wherein the human cancer patient has a HER-2 over-expressing cancer.
27 . The kit of claim 26 , wherein the HER-2 over-expressing cancer is selected from the group consisting of breast cancer, colon cancer, lung cancer, gastric cancer, pancreatic cancer, bladder cancer, cervical cancer and ovarian cancer.
28 . The kit of claim 27 , wherein the HER-2 over-expressing cancer is a breast cancer.
29 . The kit of claim 28 , wherein the breast cancer is metastatic breast cancer.