Miao Cao
Overcoming JAK/STAT-mediated CAR-T-immune-microenvironment-induced Antigen Escape in Colorectal Cancers
Abstract
FDA-approved chimeric antigen receptor T cell therapies (CARTs) have revolutionized the treatment of blood cancers. Yet none has been successful in clinical trials for “solid” tumors, such as colorectal cancer (CRC), the 2nd leading cause of all cancer deaths. CART failure in solid cancers, partly, reflects the loss of target molecules on cancer cells, but the mechanisms underlying target loss are not completely understood. Guanylate cyclase C (GCC) is a membrane receptor expressed by nearly all CRCs and is a leading immunotherapy target in CRC. While GCC-CART can effectively control some CRCs in preclinical studies, further investigation revealed poor efficacy in other models. Importantly, our preliminary data has revealed a novel bystander mechanism in which CART shapes the tumor environment (we call this CAR-TIME), causing bystander cancer cells to lose GCC. Here, we will define the mechanisms underlying CAR-TIME and explore approaches to overcome it and improve CART therapy.
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.
