Scientists at Mass General Brigham and the Broad Institute have leveraged CRISPR screens to pinpoint gene modifications that boost chimeric antigen receptor T (CAR T) cell function and persistence in multiple myeloma models. Targeting 135 genes, researchers identified CDKN1B deletion as a key alteration increasing CAR T proliferation and anti-tumor activity both in vitro and in vivo. This advance could enhance CAR T efficacy against refractory blood cancers by promoting long-term durability of therapeutic T cells.