Researchers at Massachusetts General Brigham and the Broad Institute used in vivo CRISPR screening to uncover gene targets that enhance chimeric antigen receptor (CAR) T cell function and persistence in multiple myeloma models. By targeting 135 genes, knockout of CDKN1B was found to increase CAR T cell proliferation, persistence, and anti-tumor activity. These findings may lead to improved CAR T cell therapies with greater durability and efficacy against hematologic malignancies, particularly multiple myeloma, addressing current limitations in relapse and long-term treatment success.