Distinct glutamine metabolic pathways support mitochondrial function in canine T cells 4008

Abstract Description The function of chimeric antigen receptor T (CAR T) cells is closely linked to their metabolic profile. Strategies like media conditioning and genetic modifications have been designed to optimize CAR T cell fuel selection and enhance mitochondrial metabolism, improving persistence, reducing exhaustion, and increasing anti-tumor efficacy. Canine cancer patients – with tumors resembling human malignancies – are valuable models for assessing next-generation adoptive T cell therapies. Exploring species-specific barriers, including metabolic differences not addressed during manufacturing, would allow us to optimize canine CAR T cells and better translate these findings to human therapies. We hypothesize that glutamine, with a two-fold greater concentration in canine versus human plasma, uniquely supports mitochondrial function in canine T cells. Preliminary findings indicate that canine T cells utilize less glutamine for succinyl-CoA and acetyl-CoA synthesis than human T cells, yet increased glutamine availability generates larger mitochondrial volumes, suggesting enhanced biogenesis and remodeling. Ongoing Seahorse, flow cytometry, and functional studies aim to delineate species-specific differences in glutamine-driven mitochondrial function and oxidative phosphorylation. These findings will guide strategies to condition canine CAR T cells, improve persistence and anti-tumor efficacy, and inform metabolic differences relevant to interpreting results in this comparative model. Funding Sources Supported by the Mason Cancer Research Fund. Topic Categories Veterinary and Comparative Immunology (VET)