Genome-wide CRISPR screens identify critical targets to enhance CAR-NK cell antitumor potency.

ABSTRACT: Adoptive cell therapy using engineered natural killer (NK) cells is a promising approach for cancer treatment, with targeted gene editing offering the potential to further enhance their therapeutic efficacy. However, the spectrum of actionable genetic targets to overcome tumor and microenvironment-mediated immunosuppression remains largely unexplored. We performed multiple genome-wide CRISPR screens in primary human NK cells and identified critical checkpoints regulating resistance to immunosuppressive pressures. Ablation of MED12, ARIH2, and CCNC significantly improved NK cell antitumor activity against multiple treatment-refractory human cancers in vitro and in vivo. CRISPR editing augmented both innate and CAR-mediated NK cell function, associated with enhanced metabolic fitness, increa

SUBMITTER: Biederstadt A 

PROVIDER: S-EPMC12396527 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature