Genome-wide CRISPR screens find key targets to improve cancer-killing power of engineered natural killer cells

Ablation of MED12, ARIH2, and CCNC significantly improved NK cell antitumor activity against multiple treatment-refractory human cancers.

• Genome-wide CRISPR screens in primary human NK cells identified key checkpoints that regulate resistance to immunosuppression.
• CRISPR editing enhanced both innate and CAR-mediated NK cell functions.
• Improvements in NK cell function were associated with increased metabolic fitness.
• The editing process resulted in higher secretion of proinflammatory cytokines.
• Enhanced NK cell activity led to the expansion of cytotoxic NK cell subsets.

Simplified