Researchers at the University of Texas MD Anderson Cancer Center have developed a genome-wide CRISPR screening tool named PreCiSE to identify gene targets that enhance the efficacy of chimeric antigen receptor (CAR) natural killer (NK) cell therapies. The study, published in Cancer Cell, demonstrates that editing specific genes in primary human NK cells can improve their anti-tumour activity.
PreCiSE revealed multiple checkpoints and pathways that regulate NK cell function within the tumour microenvironment, which often suppresses immune activity. By targeting and editing these genes, researchers observed strengthened innate and CAR-mediated NK cell functions, improved metabolic fitness, increased pro-inflammatory cytokine production, and expanded cytotoxic NK subsets in cancer models. The study identified three validated targets MED12, ARIH2, and CCNC that, when edited, led to enhanced NK cell activity. While these targets are significant, the broader impact of PreCiSE lies in its ability to provide an unbiased map of NK cell regulators. This platform allows for the prioritisation, editing, and combination of targets to design more effective CAR NK cell therapies across various cancer types.
The research, led by Dr. Katy Rezvani, offers new avenues for improving the efficacy of CAR NK cell therapies by leveraging targeted gene editing to overcome tumor-induced immune suppression.
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