Enhanced Antitumor Effect by Adoptive Transfer of Cytotxic T Lymphocytes Producing Interleukin-10 by Adenovirus-Mediated Gene Transduction
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Abstract:
In vivo effects of IL-10 on host antitumor immunity were tested in murine tumor models. Gene transduction of Colon 26 cells with murine IL-10 gene resulted in a marked decrease of tumorigenicity in vivo. A cell line of CD8-positive cytotoxic T lymphocytes (CD8 CTL) with strong cytolytic activity against Colon 26 wasestablished , and therapeutic effect of IL-10 gene introduction into the CD8 CTL was studied. A recombinant adenovirus Adexl CAmILl0 enabled us to achieve very efficient gene transduction and high level production of IL-10 in murine lymphocytes. IL-10 gene - transduction of CTL exerted an increased antitumor response in the adoptive treatment models, resulting in markedly reduced numbers of metastatic nodules in the lung. Our findings indicate that IL - 10 works as an immunostimulator in the adoptive transfer therapy with tumor - specific CTL.