Chemokine-tumor antigen fusion proteins as cancer vaccines

Abstract

The present invention provides a fusion polypeptide comprising a chemokine and either a tumor or viral antigen which is administered as either a protein or nucleic acid vaccine to elicit an immune response effective in treating cancer or effective in treating or preventing HIV infection.

What is claimed is:  
     
         1 . A fusion polypeptide comprising human monocyte chemotactic protein-3 and human Muc-1.  
     
     
         2 . A fusion polypeptide comprising human interferon-induced protein 10 and human Muc-1.  
     
     
         3 . A fusion polypeptide comprising human macrophage-derived chemokine and human Muc-1.  
     
     
         4 . A fusion polypeptide comprising human SDF-1 and human Muc-1.  
     
     
         5 . The fusion polypeptide of any one of  claims 1  to  4 , further comprising a spacer sequence having the amino acid sequence of SEQ ID NO:11.  
     
     
         6 . An isolated nucleic acid encoding the amino acid sequence of any one of  claims 1  to  4 .  
     
     
         7 . A vector comprising the nucleic acid of  claim 6 .  
     
     
         8 . A cell comprising the vector of  claim 7 .  
     
     
         9 . A fusion polypeptide comprising the amino acid sequence of SEQ ID NO:2.  
     
     
         10 . A fusion polypeptide comprising the amino acid sequence of SEQ ID NO:1.  
     
     
         11 . A fusion polypeptide comprising the amino acid sequence of SEQ ID NO:49.  
     
     
         12 . A fusion polypeptide comprising the amino acid sequence of SEQ ID NO:54.  
     
     
         13 . An isolated nucleic acid encoding the fusion polypeptide of any one of  claims 9  to  12 .  
     
     
         14 . A vector comprising the nucleic acid of  claim 13 .  
     
     
         15 . A cell comprising the vector of  claim 14 .  
     
     
         16 . A composition comprising the fusion polypeptide of any one of  claims 1  to  4  in a pharmaceutically acceptable carrier.  
     
     
         17 . A composition comprising the nucleic acid of  claim 6  in a pharmaceutically acceptable carrier.  
     
     
         18 . The composition of any one of claims  16  or  17 , further comprising an adjuvant.  
     
     
         19 . The composition of  claim 18 , wherein the adjuvant is an immunostimulatory cytokine.  
     
     
         20 . A composition comprising the fusion polypeptide of any one of  claims 9  to  12  in a pharmaceutically acceptable carrier.  
     
     
         21 . A composition comprising the nucleic acid of  claim 13  in a pharmaceutically acceptable carrier.  
     
     
         22 . The composition of any one of claims  20  or  21 , further comprising an adjuvant.  
     
     
         23 . The composition of  claim 22 , wherein the adjuvant is an immunostimulatory cytokine.  
     
     
         24 . A fusion polypeptide comprising a human chemokine and a human immunodeficiency virus (HIV) antigen.  
     
     
         25 . The fusion polypeptide of  claim 24 , wherein the chemokine is selected from the group consisting of IP-10, MCP-1, MCP-2, MCP-3, MCP-4, MIP 1, RANTES, SDF-1, MIG and MDC.  
     
     
         26 . The fusion polypeptide of  claim 24 , wherein the HIV antigen is selected from the group consisting of gp120, gp160, gp41, an active fragment of gp120, an active fragment of gp160 and an active fragment of gp41.  
     
     
         27 . The fusion polypeptide of  claim 24 , further comprising a spacer sequence having the amino acid sequence of SEQ ID NO:11.  
     
     
         28 . A nucleic acid encoding the fusion polypeptide of  claim 24 .  
     
     
         29 . A vector comprising the nucleic acid of  claim 28 .  
     
     
         30 . A cell comprising the vector of  claim 29 .  
     
     
         31 . A composition comprising the fusion polypeptide of  claim 24  and a pharmaceutically acceptable carrier.  
     
     
         32 . A composition comprising the nucleic acid of  claim 28  and a pharmaceutically acceptable carrier.  
     
     
         33 . The composition of any one of claims  31  or  32 , further comprising an adjuvant.  
     
     
         34 . The composition of  claim 33 , wherein the adjuvant is an immunostimulatory cytokine.  
     
     
         35 . A fusion polypeptide comprising human IP-10 and HIV gp120.  
     
     
         36 . A fusion polypeptide comprising human MCP-3 and HIV gp120.  
     
     
         37 . A fusion polypeptide comprising human MDC and HIV gp120.  
     
     
         38 . A fusion polypeptide comprising human SDF-1 and HIV gp120.  
     
     
         39 . The fusion polypeptide of any one of  claims 35  to  38 , further comprising a spacer sequence having the amino acid sequence of SEQ ID NO:11.  
     
     
         40 . An isolated nucleic acid encoding the fusion polypeptide of any one of  claims 35  to  38 .  
     
     
         41 . A vector comprising the nucleic acid of  claim 40 .  
     
     
         42 . A cell comprising the vector of  claim 41 .  
     
     
         43 . A composition comprising the fusion polypeptide of any one of  claims 35  to  38  and a pharmaceutically acceptable carrier.  
     
     
         44 . A composition comprising the nucleic acid of  claim 40  and a pharmaceutically acceptable carrier.  
     
     
         45 . The composition of any one of claims  43  or  44 , further comprising an adjuvant.  
     
     
         46 . The composition of  claim 45 , wherein the adjuvant is an immunostimulatory cytokine.  
     
     
         47 . A fusion polypeptide comprising the amino acid sequence of SEQ ID NO:6.  
     
     
         48 . A fusion polypeptide comprising the amino acid sequence of SEQ ID NO:7.  
     
     
         49 . A fusion polypeptide comprising the amino acid sequence of SEQ ID NO:5.  
     
     
         50 . A fusion polypeptide comprising the amino acid sequence of SEQ ID NO:50.  
     
     
         51 . A fusion polypeptide comprising the amino acid sequence of SEQ ID NO:52.  
     
     
         52 . A fusion polypeptide comprising the amino acid sequence of SEQ ID NO:56.  
     
     
         53 . An isolated nucleic acid encoding the fusion polypeptide of any one of  claims 47  to  52 .  
     
     
         54 . A vector comprising the nucleic acid of  claim 53 .  
     
     
         55 . A cell comprising the vector of  claim 54 .  
     
     
         56 . A composition comprising the fusion polypeptide of any one of  claims 47  to  52  and a pharmaceutically acceptable carrier.  
     
     
         57 . A composition comprising the nucleic acid of  claim 53  and a pharmaceutically acceptable carrier.  
     
     
         58 . The composition of any one of claims  56  or  57 , further comprising an adjuvant.  
     
     
         59 . The composition  claim 58 , wherein the adjuvant is an immunostimulatory cytokine.  
     
     
         60 . A method of producing an immune response in a subject, comprising administering to the subject the composition of any one of claims  16 ,  18 ,  19 ,  20 ,  22  or  23 .  
     
     
         61 . A method of producing an immune response in a subject, comprising administering to the subject the composition of any one of claims  17 ,  18 ,  19 ,  21 ,  22  or  23  under conditions whereby the nucleic acid of the composition can be expressed.  
     
     
         62 . A method of producing an immune response in a subject, comprising administering to the subject the composition of any one of claims  31 ,  33 ,  34 ,  43 ,  45 ,  46 ,  56 ,  58  or  59 .  
     
     
         63 . A method of producing an immune response in a subject, comprising adminstering to the subject the composition of any one of claims  32 ,  33 ,  34 ,  44 ,  45 ,  46 ,  57 ,  58  or  59 , under conditions whereby the nucleic acid can be expressed.  
     
     
         64 . The method of any one of  claims 60  to  63 , wherein the immune response is an effector T cell (cellular) immune response.  
     
     
         65 . A method of treating a cancer in a subject comprising adminstering to the subject the composition of any one of claims  16 ,  18 ,  19 ,  20 ,  22  or  23 .  
     
     
         66 . A method of treating a cancer in a subject, comprising administering to the subject the composition of any one of claims  17 ,  18 ,  19 ,  21 ,  22  or  23  under conditions whereby the nucleic acid of the composition can be expressed.  
     
     
         67 . A method of treating or preventing HIV infection in a subject, comprising administering to the subject the composition of any one of claims  31 ,  33 ,  34 ,  43 ,  45 ,  46 ,  56 ,  58  or  59 .  
     
     
         68 . A method of treating or preventing HIV infection in a subject, comprising administering to the subject the composition of any one of claims  32 ,  33 ,  34 ,  44 ,  45 ,  46 ,  57 ,  58  or  59 , under conditions whereby the nucleic acid can be expressed.  
     
     
         69 . A method of treating a B cell tumor in a subject, comprising administering to the subject a fusion polypeptide comprising a human chemokine and a B cell tumor antigen.  
     
     
         70 . The method of  claim 69 , wherein the B cell tumor antigen is selected from the group consisting of an antibody, a single chain antibody and an epitope of an idiotype of an antibody.  
     
     
         71 . The method of  claim 69 , wherein the human chemokine is selected from the group consisting of MCP-3, MDC and SDF-1.  
     
     
         72 . The method of  claim 69 , wherein the fusion polypeptide is selected from the group consisting of a fusion polypeptide comprising human MCP-3 and human a single chain antibody, a fusion polypeptide comprising human MDC and a human single chain antibody and a fusion polypeptide comprising human SDF-1 and a human single chain antibody.  
     
     
         73 . The method of  claim 69 , wherein the fusion polypeptide is selected from the group consisting of a polypeptide having the amino acid sequence of SEQ ID NO:51, a polypeptide having the amino acid sequence of SEQ ID NO:53 and a polypeptide having the amino acid sequence of SEQ ID NO:55.