Muc16CD is a novel CAR T cell target antigen for the treatment of pancreatic cancer

Pancreatic cancer is an aggressive malignancy with a 5-year survival rate of 13% that remains refractory to current immunotherapies, such as chimeric antigen receptor (CAR) T cells. These engineered cells can produce robust anti-tumor responses but require a reliable tumor-associated antigen (TAA) target. Here, we describe the retained ectodomain of Muc16, Muc16CD, as a novel TAA for targeting by CAR T cell therapy in pancreatic cancer. We establish clinically relevant, endogenous Muc16 and Muc16CD expression in pancreatic tumor tissues for CAR T cell targeting. Muc16CD-directed CAR T cells can both recognize and activate in a polyfunctional manner in response to patient-derived pancreatic tumor cells. Last, we demonstrate that Muc16CD-directed CAR T cells can elicit an anti-tumor response <i>in vivo</i> with significantly enhanced tumor control and survival benefits in a pancreatic tumor model. Overall, these findings demonstrate the utility of Muc16CD-targeted CAR T cell therapy in the novel setting of pancreatic cancer.