Vault Immunotherapy

Patent metadata

Field	Value
Publication number	US-2016367653-A1
Application number	US-201615256683-A
Country	US
Kind code	A1
Filing date	Sep 5, 2016
Priority date	Jul 9, 2012
Publication date	Dec 22, 2016
Grant date	—

Abstract

The invention relates to compositions of vault complexes for use as adjuvants for stimulating a cellular immune response to an antigen, for example a tumor antigen, and methods of using the vault complexes in the treatment of diseases, such as cancer.

First claim

1 . A method for stimulating a cellular immune response in a subject, comprising administering to the subject an effective amount of an antigenic peptide or an antigenic fragment or variant thereof incorporated within a vault complex.

2 . The method of claim 1 , wherein the antigenic peptide is a tumor antigen.

3 . The method of claim 1 , wherein the vault complex comprises two or more vault complexes, wherein each vault complex comprises two or more different antigenic peptides or antigenic fragments or variants.

4 . The method of claim 1 , wherein the antigenic peptide is fused to INT.

5 . The method of claim 4 , wherein the INT comprises the amino acid sequence of SEQ ID NO: 2.

6 . The method of claim 1 , wherein the antigenic peptide is fused to MVP.

7 . The method of claim 6 , wherein the antigenic peptide is fused to the N-terminus of MVP.

8 . The method of claim 1 , wherein the vault complex comprises MVP.

9 . The method of claim 8 , wherein the number of MVP is 1-78.

10 . The method of claim 8 , wherein the number of MVP is 78.

11 . The method of claim 8 , wherein the vault complex further comprises VPARP or modified VPARP, or a portion of VPARP, or a modified portion of VPARP.

12 . The method of claim 1 , wherein the cellular immune response is induction of CD8 + and CD4 + memory T-cells.

13 . The method of claim 1 , wherein the cellular immune response is production of INFγ.

14 . The method of claim 1 , further comprising administering to the subject a vault complex containing a chemokine.

15 . The method of claim 14 , wherein the chemokine is CCL21.

16 . A pharmaceutical composition for preventing or treating a subject for cancer, comprising a tumor antigen or an antigenic fragment or variant thereof incorporated within a vault complex, and at least one pharmaceutically acceptable excipient, sufficient to stimulate a cellular immune response.

17 . The pharmaceutical composition of claim 16 , wherein tumor antigen is fused to INT.

18 . The method of claim 17 , wherein the INT comprises the amino acid sequence of SEQ ID NO: 2.

19 . The pharmaceutical composition of claim 16 , wherein the antigenic peptide is fused to MVP.

20 . The pharmaceutical composition of claim 16 , wherein the vault complex comprises MVP.

21 . The pharmaceutical composition of claim 20 , wherein the number of MVP is 1-78.

22 . The pharmaceutical composition of claim 20 , wherein the number of MVP is 78.

23 . The pharmaceutical composition of claim 20 , wherein the vault complex further comprises VPARP or modified VPARP, or a portion of VPARP, or a modified portion of VPARP.

24 . The pharmaceutical composition of claim 15 , wherein the cellular immune response is induction of CD8 + and CD4 + memory T-cells.

25 . The pharmaceutical composition of claim 15 , wherein the cellular immune response is production of INFγ.

26 . The pharmaceutical composition of claim 15 , further comprising a vault complex containing a chemokine.

27 . The pharmaceutical composition of claim 26 , wherein the chemokine is CCL21.

28 . A method of preventing or treating cancer in a subject, comprising administering to the subject an effective amount of a tumor antigen or an antigenic fragment or variant thereof incorporated within a vault complex, sufficient to stimulate a cellular immune response.

29 . The method of claim 28 , wherein tumor antigen is fused to INT.

30 . The method of claim 4 , wherein the INT comprises the amino acid sequence of SEQ ID NO: 2.

31 . The method of claim 28 , wherein the antigenic peptide is fused to MVP.

32 . The method of claim 28 , wherein the vault complex comprises MVP.

33 . The method of claim 32 , wherein the number of MVP is 1-78.

34 . The method of claim 32 , wherein the number of MVP is 78.

35 . The method of claim 32 , wherein the vault complex further comprises VPARP or modified VPARP, or a portion of VPARP, or a modified portion of VPARP.

36 . The method of claim 28 , wherein the cellular immune response is induction of CD8 + and CD4 + memory T-cells.

37 . The method of claim 28 , wherein the cellular immune response is production of INFγ.

38 . The method of claim 28 , further comprising administering to the subject a vault complex containing a chemokine.

39 . The method of claim 38 , wherein the chemokine is CCL21.

40 . The method of claims 28 - 39 , wherein the administering reduces tumor volume.

41 . The method of claims 28 - 39 , wherein the administering reduces tumor growth.

42 . A method of preparing a vault complex comprising a) mixing an INT or INT fusion protein generated in insect Sf9 cells with a MVP or MVP fusion protein generated in insect Sf9 cells to generate a mixture; b) incubating the mixture for a sufficient period of time to allow formation of vault complexes, thereby generating the vault complex of claims 1 - 41 .

Assignees

• Univ California

Inventors

• Rome Leonard H
• Kickhoefer Valerie A
• Sharma Sherven
• Dubinett Steven M
• Yang Isaac
• Liau Linda M
• Kelly Kathleen A
• Yang Jian
• Kar Upendra K
• Champion Cheryl
• Jiang Janina

Classifications

• C12N2710/14043

  viral genome or elements thereof as genetic vectore · CPC title

• A61K2039/572

  cytotoxic response · CPC title

• C12Y204/0203

  NAD+ ADP-ribosyltransferase (2.4.2.30), i.e. tankyrase or poly(ADP-ribose) polymerase · CPC title

• A61K38/177 Primary

  Receptors; Cell surface antigens; Cell surface determinants · CPC title

• A61K47/6925

  the form being a microcapsule, nanocapsule, microbubble or nanobubble · CPC title