Synergistic effects of CAR T cell therapy and immune checkpoint inhibition in a clinically-relevant melanoma mouse model: implications for tumor immunity 3629

Abstract Description Immune checkpoint inhibitors (ICIs) have transformed the treatment of metastatic melanoma, yet the 5-year survival rate remains 53%. While Chimeric Antigen Receptor (CAR) T cell therapy offers tumor-specific advantages, its interaction with the endogenous immune system and combination with ICIs requires further investigation. To examine this, we used the clinically relevant YUMM 1.7 model, which has a BRAF mutation present in 50% of patient tumors and is refractory to ICI. Despite endogenous T cell infiltration, we observed that the YUMM 1.7 mouse melanoma model does not respond to PD-1 blockade alone. CAR T cell treatment effectively decreased YUMM 1.7 tumor volume, although tumors relapse about 40 days after treatment. While we have observed treatment-induced vitiligo in mice treated with CAR T cell therapy, vitiligo is increased in mice treated with the combination of CAR T cells and ICI. Combination therapy also protects against tumor relapse. Vitiligo induced by CAR T cells targeting a melanoma-irrelevant antigen hints at endogenous T cell priming and overall engagement of the endogenous immune system. CAR T cells can be found in the tumor and tumor-draining lymph node (TdLN) where mice treated with combination therapy have a higher number of CAR T cells in their TdLN, suggesting increased expansion. Ongoing studies are examining the role of T cell priming in anti-tumor activity and engagement of endogenous lymphoid and myeloid cells. Funding Sources American Society for Hematology: Hematology Inclusion Pathway Program Georgia Clinical and Translational Science Alliance Melanoma Research Foundation Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)