Researchers at Mass General Brigham and the Broad Institute leveraged CRISPR screens to identify gene knockouts that improve CAR T cell function and persistence against multiple myeloma. Using human donor-derived CAR T cells, the study pinpointed CDKN1B deletion as enhancing proliferation and antitumor activity in vitro and in vivo. This systematic genetic approach accelerates the optimization of CAR T therapies, paving the way for treatments with greater durability and effectiveness against challenging blood cancers.