Azlann Arnett
Identifying Regulators of CAR T Cell Function Using the MOTOR Platform
Abstract
Chimeric Antigen Receptor (CAR) T cell therapies are remarkably successful in B cell malignancies. In solid tumors however CAR T cells adopt a dysfunctional state after repeatedly killing tumor cells. Transcription and epigenetic factors can reprogram cells into new and unique states. To uncover key transcription and epigenetic factors that when overexpressed convert dysfunctional CAR T cells into highly potent cells that can cure patients, I developed the Model to Optimize Temporal ORFeome Responses (MOTOR) platform. I identified two leading candidates, JMJD6 an epigenetic factor that prevents a dysfunctional state, and ESRRB a transcription factor that reverses CAR T dysfunction. By evaluating the therapeutic efficacy and mechanism of JMJD6 and ESRRB enhanced CAR T cells, this study will strengthen the field’s understanding of programs that ameliorate T cell dysfunction and enable the development of CAR T therapies that target this established barrier to cure.
Watch a Q&A with Azlann
Receiving the PhRMA Foundation fellowship is an exciting step in my training as a scientist. The award will accelerate our team’s work to develop CAR T therapies that target and eliminate solid tumors, improving the lives of patients and their families.
