Abstract C065: Vaccine-enhanced adoptive cell therapy combined with one dose of platinum-based chemotherapy improves survival outcomes compared to standard of care 4-dose carboplatin in companion dogs with osteosarcoma

Abstract Background: Metastatic disease is the primary cause of death in pediatric osteosarcoma (OSA). Canine OSA is a valuable translational model as it shares many biological similarities with human OSA. There is growing evidence that combined chemo-immunotherapy improves outcomes for cancer patients. Combining the initial cytotoxic effect of platinum-based chemotherapy with the immunological effects of adoptive cell therapy (ACT) aims to increase overall response and survival rates. Instead of impairing immune function, there is increasing evidence that combining chemotherapy and an ACT can have a synergistic effect and improve outcomes in cancer patients. Methods: This prospective veterinary clinical study evaluated overall survival times of companion dogs (n=12) newly diagnosed with OSA receiving one dose of carboplatin followed by ACT initiated 21 days later. After amputation, autologous vaccination derived from their tumor was used to prime the lymphocyte response. Primed lymphocytes were collected using leukapheresis procedures, ex vivo expanded and activated, and then intravenously administered. The activated T cell infusion was followed by subcutaneous administration of interleukin-2 (20,000 IU/kg) every other day for a total of five doses. Survival time, tumor location, and other demographic data were collected. A cohort of matched controls (n=12) were selected from a data set of dogs receiving 4 doses carboplatin at 21-day intervals for newly diagnosed osteosarcoma published in the National Cancer Institute’s Canine Data Commons (n=147). Matched controls were selected using tumor location, breed, age, and weight, in order of priority. Kaplan-Meier analysis was conducted using a stratified log-rank test and a Cox proportional hazards model. Results: The one-year survival rate was 83% in the combined therapy group compared to 24% for matched controls. Median survival time (MST) was 1276 days and 198 days, respectively. The difference observed between groups was statistically significant (p = 0.003). Clinical relevance was demonstrated through improved 1-year survival rates and MST. No serious adverse events were reported in the combined therapy group. Conclusion: In the initial analysis of this prospective pilot study, dogs with OSA treated with one dose of platinum-based chemotherapy (carboplatin) followed by ACT showed improved outcomes compared to those receiving four doses carboplatin. This therapeutic approach was well-tolerated. This study provides the first data available in veterinary medicine to support improvements that chemo-immunotherapy may demonstrate over standard chemotherapy alone and provides insight into the timing and dosing of a combined approach that will establish a foundation for future studies. Results suggest chemo-immunotherapy combination may improve outcomes in canine with OSA. The translational impact of this research may have important implications for treatment of pediatric OSA. Citation Format: Jeffrey N. Bryan, Tammie Wahaus, Zachary M. Wright, Sharon Shor, Amy R. Back, Philip Bergman, Gary Wood, Wayne Carter, Barry Skikne, Tariq D. Shah, Noe Reyes. Vaccine-enhanced adoptive cell therapy combined with one dose of platinum-based chemotherapy improves survival outcomes compared to standard of care 4-dose carboplatin in companion dogs with osteosarcoma [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C065.