TREATMENT OF HUMAN HEPATOCELLULAR-CARCINOMA BY FIBROBLAST-MEDIATED HUMAN INTERFERON-ALPHA GENE-THERAPY IN COMBINATION WITH ADOPTIVE CHEMOIMMUNOTHERAPY

The therapeutic effect of the fibroblast-mediated human interferon (IF N alpha) gene therapy in combination with interleukin-2 (IL-2) activat ed killer cells (AK)/doxorubicin (i.e., adoptive chemoimmunotherapy) o n nude mice bearing the human hepatocellular carcinoma (HCC) was inves tigated, A fibroblast cell clone (NIH3T3-IFN alpha(+)) secreting 1024 U/ml human IFN alpha was obtained from 14 positive clones by BMGNeo-IN F alpha DNA transfection, G418-resistant selection, limiting dilution and assay of IFN alpha activity. After i.p. implantation of NIH3T3-IFN alpha(+) encapsulated into collagen, serum human IFN alpha activity c ould be detected from 12 h to day 15 with a peak at 72 h. AK were prep ared from human peripheral mononuclear cells costimulated in vitro by IL-2 and inactivated human SMMC 7721 HCC cells. When the NIH3T3-IFN al pha(+) cells were i.p. implanted into the HCC-bearing nude mice, the g rown of HCC was inhibited and the survival time of the mice was extend ed. The growth of HCC was inhibited more obviously when AK was i.v. in jected and IL-2 was i.p. injected after the NIH3T3-IFN alpha(+) cells had been implanted. The best therapeutic effect was achieved when NIH3 T3-IFN alpha(+) cells were used in combination with IL-2/AK/doxorubici n. All these results suggested that the fibroblast-mediated human IFN alpha gene therapy could be used to treat the human hepatocellular car cinoma effectively and that when used in combination with IL-2-based a doptive chemoimmunotherapy, the therapeutic effect would be better.