Local and systemic antitumor effect of intratumoral and peritumoral IL-12 electrogene therapy on murine sarcoma.
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Soft tissue sarcomas pose a challenge for successful treatment with conventional therapeutic methods, therefore newer therapeutic approaches are considered. In this study, we evaluated the antitumor effect of IL-12 electrogene therapy (EGT) on murine SA-1 fibrosarcoma. The therapeutic plasmid was injected either intratumorally into subcutaneous SA-1 nodules or intradermally into the peritumoral region. We achieved a remarkable local and systemic antitumor effect with both approaches after single plasmid DNA application, with significant intratumoral and systemic production of IL-12 and IFNgamma. Intratumoral IL-12 EGT resulted in over 90% complete response rate of the treated tumors with 60% of cured mice being resistant to challenge with SA-1 tumor cells. Peritumoral EGT resulted in a lower complete response rate (16%), with significant growth delay of remaining tumors. Both therapies also resulted in significant inhibition of growth of untreated tumors, growing simultaneously at a distant site. These data suggest that IL-12 EGT may be useful in the treatment of soft tissue sarcomas, exerting a local and systemic antitumor effect.