Dr. O’Connor’s research is focused on the development of genetic approaches to enhance CAR-T cell metabolic function in hostile tumor environs. Cancer cells and T cells share several metabolic features. Competition for nutrients provides a barrier for adoptively transferred T cells that rely on exogenous carbon sources to fuel their proliferation an differentiation. We study approaches to overcome nutrient depletion and oxygen deprivation; effects ultimately limiting T cell function in models of adoptive immunotherapy.
We showed how divergent fuel utilization in conjunction with CAR co-stimulation regulate the commitment to a central memory versus effector memory state during CAR-T cell differentiation. Ongoing studies will extend our understanding of this phenomenon to other CAR-related costimulatory modules.
We characterized the nutrient requirements of primary human T cells undergoing bursts of proliferation and differentiation and are developing an optimal medium formulation to enhance CAR-T cell potency.