Overview

• MD Anderson researchers created PreCiSE, a genome-wide CRISPR discovery platform tailored to primary human natural killer cells.
• The screen highlighted three validated regulators—MED12, ARIH2, and CCNC—whose disruption enhanced antitumor activity in NK and CAR NK cells.
• Editing these targets improved metabolic fitness, increased pro-inflammatory cytokine production, and expanded cytotoxic NK subsets in models resistant to treatment.
• Top hits were validated in vivo across multiple tumor models under defined immune-suppressive stressors, supporting translational potential.
• Pathway analysis shows MED12 and CCNC intersect known T-cell biology while ARIH2 appears NK-specific, guiding design choices for next-generation CAR NK therapies.