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Local and systemic antitumor effect of intratumoral and peritumoral IL-12 electrogene therapyon murine sarcoma

机译:肿瘤内和肿瘤周围IL-12电基因治疗对小鼠肉瘤的局部和全身抗肿瘤作用

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摘要

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-I fibrosarcoma.The therapeutic plasmid was injected either intratumorally into subcutaneous SA-I 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.
机译:软组织肉瘤对常规治疗方法的成功治疗提出了挑战,因此考虑使用更新的治疗方法。在这项研究中,我们评估了IL-12电基因疗法(EGT)对鼠SA-I纤维肉瘤的抗肿瘤作用,将治疗性质粒肿瘤内注射到皮下SA-I结节中或皮内注射到肿瘤周围区域中,我们获得了显着的局部单一质粒DNA施用后两种方法均具有抗肿瘤和全身抗肿瘤作用,并且在肿瘤内和全身产生IL-12和IFNgamma。肿瘤内IL-12 EGT导致治疗肿瘤的完全缓解率超过90%,治愈的小鼠中有60%抵抗SA-1肿瘤细胞的攻击。胃周EGT导致较低的完全缓解率(16%),其余肿瘤明显延迟生长。两种疗法还导致未治疗肿瘤的生长受到明显抑制,并在远处同时生长。这些数据表明IL-12 EGT可能在治疗软组织肉瘤中发挥作用,发挥局部和全身性抗肿瘤作用。

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