Combination Immunogene Therapy
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.