LAUSR

When cells or tissues are exposed to an electric field, structural changes can be induced in the cell membrane, allowing molecules to flow into the cells. This condition is useful for delivering cytotoxic drugs whose transport into cells is impeded, such as bleomycin and cisplatin. This is referred to as electrochemotherapy (ECT). When DNA or RNA molecules are transported into cells, the approach is called gene electrotransfer (GET). ECT is an effective local treatment for tumors, but it lacks the systemic component of treatment that is essential for fighting metastatic disease. Cancer progression and metastasis are closely related to an inadequate antitumor immune response. Therefore, the antitumor efficacy of interleukin 12 (IL -12), a cytokine that stimulates the innate and adaptive immune response, has been tested in preclinical studies using plasmid DNA encoding IL -12 delivered into the tumor by gene electrotransfer (IL -12 GET). In addition, the combined treatment of ECT and IL -12 GET has already been shown to be effective in the treatment of mouse tumors and has been used in clinical trials in companion dogs to treat various histological types of spontaneous tumors. The results of these studies showed that the treatment is safe and effective. However, in these clinical trials, IL -12 GET was administered by different routes, either intratumorally (i.t.) or peritumorally (peri.t.). Therefore, the aim of this study was to compare the two IL -12 GET routes of administration in combination with ECT and to determine their contribution to the enhanced response to ECT. In the clinical trial, 59 dogs with spontaneous mast cell tumors (MCT) were divided into two groups: one group was treated with the combination of ECT and GET peri.t. (29 dogs) and the other with the combination of ECT + GET i.t. (30 dogs). The efficacy of the treatment was compared with the group of 18 dogs treated with ECT alone. In addition, immunohistochemical studies of tumor samples before treatment and flow cytometric studies of PMBC before and after treatment were performed to determine immunological aspects of the treatment. The results of this study showed that local tumor control was significantly better in the ECT + GET i.t. group (p < 0.05) than in the ECT + GET peri.t. and ECT groups. In addition, the disease-free interval (DFI) and progression-free survival (PFS) were significantly longer in the ECT + GET i.t. group than in the other two groups (p < 0.05). The data on local tumor response, DFI and PFS were consistent with immunological studies, as we detected increased infiltration of antitumor immune cells after treatment in the ECT + GET i.t. group, also suggesting a systemic effect. Citation Format: Maja Cemazar, Ursa Lampreht Tratar, Nina Milevoj, Katarina Znidar, Katja Ursic Valentinuzzi, Andreja Brozic, Gregor Sersa, Natasa Tozon. Electrochemotherapy and IL-12 gene electrotransfer in treatment of mast cell tumors in companion dogs. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5122.