Electrochemotherapy and gene electrotransfer in veterinary oncology

Abstract

Veterinary medicine has become an important translational bridge from in vitro and preclinical studies to human medicine, offering invaluable model for research in naturally occurring diseases and therefore providing vital data which cannot be gained from strictly experimental animal models. This is especially true for investigating novel approaches to cancer treatment. Electrochemotherapy and gene electrotransfer are two such novel treatment options in both human and veterinary clinical oncology. Current research shows that electrochemotherapy has excellent local ablative effect on treated tumors. However, its major drawback lies in its inability for any type of systemic antitumor effect. Therefore, one possibility to boost its effect is combining electrochemotherapy with systemic immunomodulatory effects of interleukin-12 (IL-12) gene electrotransfer, since both use the same platform technology, electroporation. In veterinary medicine, the combined treatment was successfully used in different types of tumors in dogs and horses, providing excellent local antitumor control with indications of systemic effects of such treatments, clinically seen as prolongation of treated patients' lifespan, distant effect on untreated tumors, lymph node metastases, and regression of invasive tumor growth. Furthermore, immunologic studies show that this type of treatment causes systemic induction of patient's immune response as seen from flow cytometry of treated patients' blood showing temporary increase of circulating cluster of differentiation 8 positive (CD8+) cells after each therapeutic session.With use of IL-12-based gene therapy, several important safety aspects should be observed, mainly possible IL-12 toxicity and environmental safety of this type of therapy, regarding possible shedding of antibiotic resistance genes into environmental bacteria.