Miao Cao
Boosting the Efficacy of CAR T Cell Therapy for Colorectal Cancer
Summary
Chimeric antigen receptor (CAR) T cell therapies have revolutionized the treatment of blood cancers. Yet none have been successful in clinical trials for “solid” tumors, such as colorectal cancer (CRC), the second leading cause of all cancer deaths. CAR T cell therapy reprograms a patient’s own T cells to find and kill cancer cells by targeting specific surface markers (antigens). Guanylate cyclase C (GCC) is a membrane receptor expressed by nearly all CRCs and is a leading target for CAR T cell therapy development in CRC. Preclinical studies have shown mixed success. Failure of CAR T cell therapy in solid tumors reflects in part the loss of target antigens on cancer cells, but the mechanisms underlying this target loss are not fully understood. We have identified a novel mechanism by which CAR T cell therapy shapes the tumor environment (we call this CAR-TIME), causing cancer cells to lose the target antigen, GCC. Our project will further define the mechanisms underlying CAR-TIME and explore approaches to overcome it and improve CAR T cell therapy for CRC.
I am thrilled to receive the predoctoral fellowship from the PhRMA Foundation. This honor supports my research on boosting CAR-T cell efficacy for cancer patients and advances my career aspirations in translational medicine.
