Abstract
Interleukin-12 (IL-12) is a potent antitumor cytokine, which induces and enhances the activity of natural killer (NK) cells, lymphokine activated killer (LAK) cells and cytotoxic T lymphocytes (CTL). IL-12 also stimulates IFN-γ production from both T cells and NK cells. In this study, we transfected methylcholanthrene-induced fibrosarcoma (MCA-D) with TNF gene and investigated the therapeutic effect of TNF gene-transduced cancer vaccine and whether the vaccination effect is enhanced by systemic administration of recombinant IL-12 (rIL-12), in a murine model. TNF gene-transduced cancer vaccine or systemic administration of rIL-12 showed slight or moderate inhibition of pre-established tumor. However, simultaneous application of the vaccine and rIL-12 resulted in complete eradication. The cytotoxicity of CTL against parental tumor cells was enhanced with the combination of the vaccine and rIL-12, and IFN-γ production from spleen cells also increased synergistically. Our findings show that synergistic enhancement of CTL activity and IFN-γ production could play an important role in the antitumor effect of combination therapy using TNF gene-transduced cancer vaccine and rIL-12.
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Taniguchi, F., Yamagishi, H., Fujiwara, H. et al. Systemic administration of rIL-12 synergistically enhances the therapeutic effect of a TNF gene-transduced cancer vaccine. Gene Ther 5, 1677–1684 (1998). https://doi.org/10.1038/sj.gt.3300779
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DOI: https://doi.org/10.1038/sj.gt.3300779