Antitumor Effects Of Human Interferon-Alpha Gene Therapy In Melonoma

Interferon(IFN) is a pleiotropic immunoregulatory cytokine and has been certified to be used in clinic in more than forty countries. As other cytokinies, it results in sever side effects. So its clinical application has been limited. The shortcoming could be overcome by IFN-α gene therapy. At first, the tumor cells which had been genetically engineered to secrete IFN-α could be implanted. The tumorigenicity of the tumor cells decreased obviously. Second, the carrier cells such as fibroblast cells which had been genetically engineered to secrete IFN-αcould be implanted and secrete IFN-α constitutively in vivo. The good results may be gottont and the sied effects may be decreased. In the present study, IFN-α gene was transfered into M21 melanoma cells,Tca8113 squamouse carcinoma cells and fibroblast cells and its anti-tumor effects were observed. Human IFN-α gene was transfered into human melanoma cells(M21) mediated by liposone. The M21 cell clone secreting the highest IFN-α level was obtained after G418 resistance selection, limiting dilution and the assay of IFN-α activity. After the nude mice were inoculated subcutaeously with the M21-IFN-α+ cells,we had found the tumor growth was inhibited and the survival period of the nude mice extended when compared with the nude mice inoculated with the wild-type M21. On the other hand, We used the NIH3T3 fibroblast cells as carrier because the cell clone is easy to expand ,to be transfered and to express the exogenous gene. We established a moded of fibroblast cell-mediated human IFN-α geng therapy to anti-melonoma. BMGNeo-IFN-α DNA was transfered into NIH3T3 fibroblast cells by the liposome method. So the clone secreting the hightest level of IFN-αwas selected. The cell clone was expanded in vitro,encapsulated into collagen and implanted i.p.into mice. Serum IFN-α activity could be detected from 12 hours and sustained for a long time. These results demonstrated that fibroblasts could successfully transfer and express the hIFN-α gene in vivo. We used the model to treat the nude mice inoculated with melouoma and found that the growth of of M21 cells were inhibited obviously. All these results suggested that the fibroblast cell-mediated gene therapy could be used to treat the human melonoma and when used in combination with operation, the therapeutic effect would be better.