Researchers at Mass General Brigham and the Broad Institute have leveraged in vivo CRISPR screens to discover genetic modifications that improve the persistence and function of CAR T cells in treating multiple myeloma. By targeting 135 genes, the team identified regulators such as CDKN1B, whose deletion enhances CAR T proliferation and anti-tumor activity. This approach addresses challenges in CAR T cell therapies, particularly for refractory cancers, by optimizing T cell survival in physiological contexts. The study paves the way for engineering more durable and effective immunotherapies.