20.500.12556/DiRROS-15569 Potentiation of electrochemotherapy effectiveness by immunostimulation with IL-12 gene electrotransfer in mice is dependent on tumor immune status Electrochemotherapy (ECT) exhibits high therapeutic effectiveness in the clinic, achieving up to 80% local tumor control but without a systemic (abscopal) effect. Therefore, we designed a combination therapy consisting of ECT via intratumoral application of bleomycin, oxaliplatin or cisplatin with peritumoral gene electrotransfer of a plasmid encoding interleukin-12 (p. t. IL-12 GET). Our hypothesis was that p. t. IL-12 GET potentiates the effect of ECT on local and systemic levels and that the potentiation varies depending on tumor immune status. Therefore, the combination therapy was tested in three immunologically different murine tumor models. In poorly immunogenic B16F10 melanoma, IL-12 potentiated the antitumor effect of ECT with biologically equivalent low doses of cisplatin, oxaliplatin or bleomycin. The most pronounced potentiation was observed after ECT using cisplatin, resulting in a complete response rate of 38% and an abscopal effect. Compared to B16F10 melanoma, better responsiveness to ECT was observed in more immunogenic 4%T1 mammary carcinoma and CT26 colorectal carcinoma. In both models, p. t. IL-12 GET did not significantly improve the therapeutic outcome of ECT using any of the chemotherapeutic drugs. Collectively, the effectiveness of the combination therapy depends on tumor immune status. ECT was more effective in more immunogenic tumors, but GET exhibited greater contribution in less immunogenic tumors. Thus, the selection of the therapy, namely, either ECT alone or combination therapy with p. t. IL-12, should be predominantly based on tumor immune status. electrochemotherapy gene electrotransfer interleukin-12 elektrokemoterapija elektroprenos genov interlevkin-12 true false true Elsevier Angleški jezik Slovenski jezik by Authors Neznano 2022-09-21 03:35:25 2022-09-21 14:40:06 2022-09-30 15:08:05 0000-00-00 00:00:00 2021 0 0 str. 623-635 no. 21 Vol. 332 Apr. 2021 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 2021-03-08 602.6/.7 0168-3659 10.1016/j.jconrel.2021.03.009 54492931 RAZ_Ursic_Valentinuzzi_Katja_2021.pdf RAZ_Ursic_Valentinuzzi_Katja_2021.pdf 1 53FD7CD78C93640F8B5DBCA4938228C4 12ad2728e7f37d42c4a078b8c3cf1fed7d35b57939336df35852cf51fe32ba98 b06558a3-3999-11ed-bea5-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=20606 Onkološki inštitut Ljubljana 0 0 0