CAR mast cell for solid tumor

Summary Chimeric Antigen Receptor (CAR)-T cell therapies have achieved unprecedented success in treating blood cancers that are resistant to traditional radiation or chemotherapies. However, the efficacy of CAR-T therapy to solid tumors remains limited. Major challenges include poor infiltration of T cells into tumors, exhaustion and low persistence of T cells under a hostile tumor environment. To tackle these problems, we aim to seek alternative cell carriers for CAR. Mast cells present several advantages in targeting solid tumors: they reside in tumor tissues and can live up to years. They can repetitively kill target cells without exhaustion. They also release cytokines that can recruit other effector cells to kill cancer. In this project, we will design CARs that specifically activate mast cells to kill solid tumors, using melanoma and colon cancer as models. Our efforts are expected to lay the scientific foundation for a brand-new cell therapy, and provide rationales and generate reagents for moving towards further pre-clinical and clinical studies.