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Retrovirus-mediated gene transfer of the cytokine genes interleukin-1b and tumor necrosis factor-a into human neuroblastoma cells: consequences for cell line behavior and immunomodulatory properties. |
European Cytokine Network. Volume 12, Number 1, 78-86, March 2001, Articles originaux
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 Free Article
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Author(s) : C. Coze, T. Leimig, M.T. Jimeno, P. Mannoni |
Summary : We have investigated the value of a gene therapy approach for neuroblastoma (NB), based on retroviral transduction of the IL-1b or TNF-a cytokine genes into human NB lines. Secretion of the corresponding cytokine, was demonstrated in all lines, although with considerable quantitative variations. Cytokine gene expression significantly reduced the proliferation index (p = 0.0001); this effect was associated with either terminal neuronal (one TNF-a line) or fibroblast-like differentiation (two IL-1b lines), leading to growth arrest after a few weeks. Cell surface levels of CD54 and HLA class II remained unaffected, but HLA class I (p < 0.001) and CD58 expression (p = 0.01) increased on SKNSH after TNF-a gene transfer. Mononuclear cells from normal allogeneic donors cocultured with both IL-1b (p < 0.001) and TNF-a lines (p < 0.01), showed a significant increase in the proportion of activated T cells (CD3+DR+); however, their cytotoxicity and proliferation rate remained unchanged. Immunotherapy of neuroblastoma will require identification of transduced lines in which cytokine secretion induces phenotypic changes in such a way as to augment their likely immunomodulatory properties without impeding cell growth. Because of the limited efficacy of IL-1b or TNF-a gene transfer alone, further studies should focus on combination with other immunomodulatory agents, to improve their potential efficacy in neuroblastoma. |
Keywords : neuroblastoma, immunotherapy, gene therapy, cytokine, IL-1b, TNF-a. |
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