Researchers from Mass General Brigham and the Broad Institute employed in vivo CRISPR screening to identify gene knockouts that significantly improve CAR T cell function and persistence against multiple myeloma. Targeting 135 genes, the study uncovered that deletion of the cell cycle regulator CDKN1B notably enhances T cell proliferation, survival, and anti-tumor activity in mouse models. This breakthrough offers a pathway to enhance immunotherapy efficacy for hematological malignancies by genetically optimizing engineered T cells.