Vault Immunotherapy

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.

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 .