Abstract B33: Immuno gene therapy with IL-12 combined with electrochemotherapy for the treatment of skin and oral tumors in client-owned dogs
Authors: Cemazar Maja , Tratar Ursa Lampreht , Milevoj Nina , Brozic Andreja , Nemec Ana , Sersa Gregor , Tozon Natasa 
Published: March 2020

Abstract
Cancer is a common disease of client-owned dogs, with the majority of solid tumors located in the skin or oral cavity. One of the local ablative therapy is electrochemotherapy, where cytotoxic drugs, bleomycin or cisplatin, are introduced into the cells by application of electric pulses (electroporation). In veterinary oncology, electrochemotherapy proved to be an effective and safe local treatment of tumors in horses, cats, dogs, and exotic animals, where success is comparable to standard surgical therapy. The drawback of electrochemotherapy is that, despite its high local effectiveness, it does not have systemic antitumor effects. In preclinical and some clinical studies, gene electrotransfer (GET) of plasmid encoding IL-12 was effective local therapy eliciting also systemic immune response. By means of electroporation, the plasmid DNA is introduced into the cells, resulting in IL-12 expression. The aim of our study was to evaluate a combination of electrochemotherapy and GET of plasmid encoding canine IL-12 for the treatment of skin and oral tumors in dogs. From June 2015 till October 2018, 51 dogs were enrolled in the clinical study: 38 dogs with 68 skin tumors and 13 dogs with oral tumors. Under general anesthesia, electrochemotherapy and gene therapy with IL-12 were performed. For electrochemotherapy cytotoxic drugs were first administered: bleomycin intravenously or intratumorally or cisplatin intratumorally. Standard electrochemotherapy pulses (8 electric pulses, 100 μs, 1300 V/cm, 5 kHz) were applied 10 minutes after intravenous bleomycin administration and immediately after intratumoral bleomycin or cisplatin administration. After electrochemotherapy, the plasmid pCMVcaIL-12 was applied peritumorally at two sites of the tumor and immediately after application of plasmid DNA the electric pulses were applied, using noninvasive electrodes with 7 pins arranged in hexagonal arrays with central pin (24 pulses, 60 V, 150 ms, 0.40/1.39 Hz). The results of our study showed that the combination of electrochemotherapy and gene therapy of plasmid IL-12 is the most effective in treatment of skin tumors, especially in the case of mast cell tumors, with ~90% of local tumor control rate. Moreover, in the case of skin tumors we demonstrated an effect in distant untreated tumors in 5 dogs, which confirms the systemic (abscopal) effect of the therapy. In the treatment of oral tumors, we achieved 54% of objective local tumor response 1 month after treatment. Although progressive disease occurred in 11/13 patients at the end of observation period, a mean survival time of 7 months was obtained, which is comparable with standard surgical therapy, but without cosmetic or functional shortcomings that occur after surgical treatment. To conclude, the results of our study showed significant antitumor response of combined therapy in the case of skin tumors. Also, for dogs with oral tumors combined therapy represents a valuable treatment option, especially when other treatment approaches are not applicable or acceptable.
Citation Format: Maja Cemazar, Ursa Lampreht Tratar, Nina Milevoj, Andreja Brozic, Ana Nemec, Gregor Sersa, Natasa Tozon. Immuno gene therapy with IL-12 combined with electrochemotherapy for the treatment of skin and oral tumors in client-owned dogs [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B33.