Overview

• Two complementary Nature studies used large-scale in vivo CRISPR screening to find gene knockouts that improve CAR T cell persistence and antitumor activity.
• CeMM’s CELLFIE platform flagged RHOG as a potent knockout in leukemia models, yielding CAR T cells that expanded better, resisted exhaustion, and controlled disease.
• Combining RHOG and FAS knockouts produced synergistic benefits in mice, including faster expansion, reduced fratricide, and cures in aggressive leukemia models.
• Mass General Brigham and Broad screened 135 genes across a T cell’s lifecycle and found that deleting CDKN1B increased proliferation, long-term persistence, and efficacy in a myeloma model.
• The studies showed key divergences between in vitro and in vivo results, underscoring the need for animal validation before advancing edits toward safety testing and potential clinical evaluation.