Innovative Approaches to Enhance Chimeric Antigen Receptor (CAR) T Cell Potency Using Quiescent T Cells

My research focuses on developing Chimeric Antigen Receptor (CAR) T cells for adoptive immunotherapy. The goal of theresearch is to enhance the efficacy of CAR T therapy by developing potent of CAR T cells. Another goal of this research is toshorten the CAR T manufacturing period to increase the availability of this therapy in resource constraint health care settings, aswell those patients with rapidly progressive disease. CAR T cells are generated by transducing activated T cells with lentiviralvectors and expanding their progeny over 9-14 days. T cells progressively differentiate over time. Transducing quiescent T cellswith CAR will preserve the intrinsic stem-like properties of nave and memory T cells. This approach will yield CAR T cells withenhanced replicative capacity, engraftment, and in vivo activity. The purpose of this work is to determine the optimal T cell subsetand corresponding optimal costimulatory domain for CAR when it is expressed in quiescent T cells. The scope of this research isthat CAR T cells generated by transducing quiescent T cells will preserve the intrinsic stem-like properties of nave and memory Tcells. This approach will yield CAR T cells with enhanced replicative capacity, engraftment and in vivo activity. The goal of thestudy is to determine how co-stimulation in the context of a CAR, expressed in quiescent T cell subsets, influences proliferation,metabolism, and effector function in xenograft models of ALL.