Preclinical study of an optimized AAV cancer vaccine in a spontaneous canine model of oral melanoma.

Like humans, companion dogs develop cancers spontaneously in the context of increased age, genetic variations, or environmental exposures, making them valuable as a preclinical model. Here, we assessed the safety and preliminary effectiveness of a multivalent adeno-associated virus (AAV) cancer vaccine in spontaneous canine oral melanoma. Eight companion dogs were vaccinated with equal doses of three different optimized AAV vectors encoding the melanoma others glycoprotein 100 (GP100), tyrosinase (Tyr), and tyrosinase-related protein 1 (TRP-1). Five dogs received a dose of 3 × 1012 viral genomes (vg)/dog, and three others received 9 × 1012 vg/dog. Post-vaccination monitoring established a lack of adverse effects and confirmed the presence of antigen-specific IFN-γ-producing T cells in the blood of most dogs. Although the variable survival times make it difficult to evaluate the effectiveness of the optimized AAV cancer vaccine at this point, three of the eight dogs were disease-free by the end of study, and two dogs survived 804 and 953 days after vaccination, and one is currently alive. Thus, the optimized AAV cancer vaccine showed promise in a spontaneous cancer animal model that closely recapitulates human disease development.