Combination Immunogene Therapy

Abstract

The present invention provides to immunogene therapy protocols for the treatment of tumors. In particular, the present invention provides combinations of immune-modulating proteins that induce systemic immunity against tumors. In addition, the present invention provides humanized animal models suitable for the evaluation of anti-human tumor immunity and permit the identification of combinations of immune-modulating genes which when delivered to human tumor cells induce an effective anti-tumor response, including a systemic anti-tumor response.

1 . A tumor cell composition comprising a tumor cell modified to express a B7-2 protein and at least one additional immune modulator, or a functional fragment of said B7-2 protein or said immune modulator. 
     
     
         2 . The tumor cell composition according to  claim 1 , wherein said at least one additional immune modulator is a cytokine protein. 
     
     
         3 . The tumor cell composition according to  claim 2 , wherein said cytokine protein is selected from the group consisting of interleukin 2, interleukin 4, interleukin 6, interleukin 7, interleukin 12, granulocyte-macrophage colony stimulating factor, granulocyte colony stimulating factor, interferon-gamma, and tumor necrosis factor-alpha. 
     
     
         4 . An expression vector comprising a polynucleotide sequence encoding a B7-2 protein and at least one additional immune modulating protein, or a functional fragment of said B7-2 protein or said immune modulator. 
     
     
         5 . The expression vector according to  claim 4 , wherein said at least one additional immune modulating protein is a cytokine protein. 
     
     
         6 . The expression vector according to claim  22 , wherein said cytokine protein is selected from the group consisting of interleukin 2, interleukin 4, interleukin 6, interleukin 7, interleukin 12, granulocyte-macrophage colony stimulating factor, granulocyte colony stimulating factor, interferon-gamma, and tumor necrosis factor-alpha. 
     
     
         7 . The expression vector according to  claim 4 , wherein said expression vector is a viral vector. 
     
     
         8 . The expression vector according to  claim 7 , wherein said viral vector is a retroviral vector or an adenoviral vector. 
     
     
         9 . The expression vector according to  claim 4 , wherein said expression vector is encapsulated by, or complexed with, a liposome. 
     
     
         10 . A method for the treatment or prevention of cancer comprising administering to a subject in need thereof an effective amount of a tumor vaccine comprising a tumor cell modified to express a B7-2 protein and at least one additional immune modulator, or a functional fragment of said B7-2 protein or said immune modulator. 
     
     
         11 . The method according to  claim 10 , wherein said at least one additional immune modulator is a cytokine protein. 
     
     
         12 . The method according to  claim 11 , wherein said cytokine protein is selected from the group consisting of interleukin 2, interleukin 4, interleukin 6, interleukin 7, interleukin 12, granulocyte-macrophage colony stimulating factor, granulocyte colony stimulating factor, interferon-gamma, and tumor necrosis factor-alpha. 
     
     
         13 . The method according to  claim 10 , wherein said cancer cells are from a tumor. 
     
     
         14 . The method according to  claim 13 , wherein said cancer cells are from a brain tumor or from melanoma. 
     
     
         15 . The method according to  claim 14 , wherein said brain tumor is a glioblastoma.