Funded by the 2019 Wine Celebration Fund a Need for Canine Comparative Oncology
Osteosarcoma (OS) is a common and devastating cancer of the bone which occurs in both dogs and humans. Upon diagnosis, the majority of dogs require amputation and chemotherapy. Despite this, most relapse within a year of diagnosis. In humans, OS is the most common bone tumor of adolescents and young adults (AYA). Pediatric and AYA patients with metastatic OS at diagnosis or who relapse after frontline therapy have an extraordinarily poor prognosis, with only a 20-30% survival at 5-years. Despite concerted attempts, these outcomes have not changed in >25 years.
Due to similarities in genetics, biologic behavior and treatment responses, canine OS is considered the best model of pediatric and AYA OS. We have used this model to investigate new immunotherapies and some of these have been translated into human trials (NCT03900793). In preliminary studies, we have determined that canine OS overexpress a protein known as B7-H3, which is absent in normal dog tissues (heart, liver, brain, kidney and spleen). We also find that both dog and human OS are infiltrated with tumor associated macrophage (TAM), which suppress immune responses to the tumor. The Dow lab has designed and tested methods to deplete these TAMs and the Verneris lab has been testing ways to target B7H3 using cellular immunotherapy with chimeric antigen receptors (CARs). Here, we will bring these two approaches together to test whether the improve outcomes in rodent xenograft models and in pet dogs with macroscopic pulmonary OS metastases in a clinical trial at CSU.
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