METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER

• US 20150283220A1
• Filed: 10/16/2013
• Published: 10/08/2015
• Est. Priority Date: 10/19/2012
• Status: Abandoned Application

• Current Assignee: Bavarian Nordic A/S
• Original Assignee: Bavarian Nordic Inc. (Bavarian Nordic A/S)
• Inventors: Mandl, Stefanie, Delcayre, Alain, Rountree, Ryan
• Application Number:
  US14/435,891
• Publication Number:
  US 20150283220A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/5256 expressing foreign proteins
• CPC Class Codes: A61K 39/001106 Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ErbB4
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/24134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2710/24143 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

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.

Claims

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.