Researchers from Mass General Brigham and the Broad Institute utilized comprehensive CRISPR genetic screens to identify key gene knockouts that significantly improve CAR T cell proliferation, persistence, and anti-tumor activity, particularly in multiple myeloma models. Deletion of CDKN1B, a cell cycle regulator, notably enhanced CAR T functionality both in vitro and in vivo. This approach accelerates the systematic discovery of genetic modifications to boost engineered T cell therapies, potentially overcoming current limitations such as reduced long-term efficacy and failure in solid tumors, representing a crucial advance in immuno-oncology.