Potentiation of electrochemotherapy effectiveness by immunostimulation with IL-12 gene electrotransfer in mice is dependent on tumor immune status

• DOI: 10.1016/j.jconrel.2021.03.009
• Publication Date: 2021-03-08T23:58:08Z
• Authors: Katja Ursic; Spela Kos; Urska Kamensek; Maja Cemazar; Simona Miceska; Bostjan Markelc; Simon Bucek; Barbara Staresinic; Veronika Kloboves...; Richard Heller; Gregor Sersa
• Keywords: Electrochemotherapy; Combination therapy

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 combination therapy consisting of ECT via intratumoral application bleomycin, oxaliplatin or cisplatin with peritumoral gene electrotransfer plasmid encoding interleukin-12 (p. t. IL-12 GET). Our hypothesis was that p. GET potentiates effect on and levels potentiation varies depending immune status. tested three immunologically different murine models. In poorly immunogenic B16F10 melanoma, potentiated antitumor biologically equivalent low doses cisplatin, bleomycin. The most pronounced observed after using resulting complete response rate 38% an abscopal Compared better responsiveness more 4 T1 mammary carcinoma CT26 colorectal carcinoma. both models, did not significantly improve outcome any chemotherapeutic drugs. Collectively, depends effective tumors, exhibited greater contribution less tumors. Thus, selection therapy, namely, either alone IL-12, should be predominantly based