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

被引:41
作者
Pavlin, Darja [2 ]
Cemazar, Maja [1 ]
Kamensek, Urska [1 ]
Tozon, Natasa [2 ]
Pogacnik, Azra [2 ]
Sersa, Gregor [1 ]
机构
[1] Inst Oncol Ljubljana, Dept Expt Oncol, Ljubljana, Slovenia
[2] Univ Ljubljana, Vet Fac Ljubljana, Ljubljana, Slovenia
关键词
electroporation; electrogene therapy; sarcoma; IL-12; tumor; skin; INTERLEUKIN-12; GENE-THERAPY; IN-VIVO ELECTROPORATION; INTRAMUSCULAR ELECTROPORATION; HEPATOCELLULAR-CARCINOMA; EXPRESSION PLASMIDS; ADENOVIRAL VECTOR; DELIVERY; GROWTH; DNA; COMBINATION;
D O I
10.4161/cbt.8.22.9734
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
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 IFN gamma. 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-I 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.
引用
收藏
页码:2114 / 2122
页数:9
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