Opportunities in immunotherapy for human and canine melanoma

Abstract

Both in humans and dogs (metastatic) melanoma is a common and aggressive disease for which established treatment methods have not been proven curative. The treatment for human melanoma patients has seen incredible changes over the past few years due to the development and approval of targeted agents, such as BRAF and MEK inhibitors, and new methods of immunotherapy. Over the last few years a large number of immunotherapy options have been proposed and trialed. The present literature study describes these promising immune-based therapies for human melanoma, namely cytokines, monoclonal antibodies (anti-CTLA4 and anti-PD1), cancer vaccines, and adoptive cell therapy, and their most important results. At this point several of these immune-based drugs, like CTLA-4 antibodies and PD-1 antibodies, have demonstrated to induce long term responses in a section of patients and have been approved, while several others are in different stages of development. Challenges that can accompany immunotherapy include a low response rate, a delay in effects, adverse effects, and high costs. An overview of the clinical trials conducted with immune-based drugs for canine melanoma is also given. To date only the DNA-based canine melanoma vaccine has been approved and many other immunotherapy methods using (non)viral vectors to deliver gene products or cytokine producing cells have been studied. In general, adverse events were minor or absent and treated patients often showed an improved course of disease and survival times. This suggests their usefulness as adjuvant treatment options for canine melanoma. Outcomes obtained in canine melanoma clinical trials can serve as a good preclinical proof of concept and evaluate safety for human immunotherapy trials. The major strengths of a canine model are the significant similarities in melanoma biology and the spontaneous occurring of the disease in a species that is immune competent, outbred and lives in an environment that is similar to humans.