Targeting Synovial Sarcoma with Cancer Testis Antigen Incorporated Oncolytic Viruses

Synovial sarcoma is an aggressive soft tissue tumor that disproportionately affects the young adult population. The average age at diagnosis is 26 years, and 40%-60% of patients are alive at 5 years. Immune checkpoint inhibition antibodies and vaccine-based approaches have failed to demonstrate meaningful benefit in this deadly disease. Targeting synovial sarcoma with replication-competent oncolytic measles and vesicular stomatitis viruses tailored to express both an immune stimulant and a highly expressed protein in synovial sarcoma may render the disease susceptible to immune-mediated death. We propose to accomplish this task by testing our engineered novel oncolytic measles and vesicular stomatitis viruses that incorporate both the potent immune stimulator neutrophil activating protein (NAP) and the highly synovial sarcoma expressed antigen New York esophageal squamous cell carcinoma-1 (NY-ESO-1). In addition to characterizing the activity of the viruses, we will evaluate a combinatorial approach, pairing both viruses with immune checkpoint inhibitors to determine if we can overcome the resistance to immune checkpoint inhibition in synovial sarcoma. The young age of onset and more common occurrence of sarcomas in the military personnel, as compared with the general population, render our research highly relevant to our Service Members and their dependent children. Our team has a track record of expeditiously translating oncolytic virotherapy from the bench to the clinic. The data generated herein will change the paradigm for future immunotherapeutic approaches to the treatment of synovial sarcoma.