My research program is aimed at developing novel ways to use the immune system to treat cancer. Our laboratory work focuses on deconstructing the mechanisms underlying immune suppression and developing novel therapies to overcome them. The laboratory uses a multi-pronged approach to enhance the immune response to cancer by (1) exploring immune modulation (checkpoint blockade and co-stimulation), (2) using chemotherapy, radiation therapy, and targeted therapies to elicit tumor antigen release and modulate the immune system, (3) improving vaccine strategies to deliver antitumor immunity (alphavirus particles and oncolytic viruses), and (4) combining immune modulation with small molecule inhibitors, vaccines, chemotherapy, and radiation. Another area of focus is the identification of genetic lesions in melanoma for which targeted therapy can be evaluated in both human tumor specimens and mouse models of spontaneous melanoma. Work from the laboratory has generated several clinical trials that have progressed to pivotal phase III trials, as well as to the first licensure of a therapeutic cancer vaccine in companion animals. I led a phase III study of ipilimumab, a checkpoint blocking antibody, which resulted in its FDA approval for patients with melanoma and led the development of novel response criteria for immunotherapies. Most recently, I led a phase I trial of combined CTLA-4 and PD-1 blockade in melanoma, which demonstrated a response rate of 40%. Phase II and III studies aimed at demonstrating the value of combination blockade are ongoing under our group’s leadership. Based on preclinical data, we initiated the first in-human trial with an anti-GITR antibody.