Cancer cell

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

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated

Abstract

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.

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Funding

Competing interests

Declaration of interests R.B., N.U., May Daher., H.R., P.B., S.A., M.S., Paul Lin., Y.L., E.L., E.J.S., K.R., and The University of Texas MD Anderson Cancer Center have an institutional financial conflict of interest with Takeda Pharmaceuticals. R.B., S.A., E.L., E.J.S., K.R. and The University of Texas MD Anderson Cancer Center have an institutional financial conflict of interest with Affimed. K.R. participates on the Scientific Advisory Board for Avenge Bio, Virogin Biotech, Navan Technologies, Caribou Biosciences, Bit Bio Limited, Replay Holdings, oNKo Innate, The Alliance for Cancer Gene Therapy ACGT, Innate Pharma and Shinobi Therapeutics. K.R. is the scientific founder of Syena. May Daher participates on the Scientific Advisory Board of Cellsbin. E.J.S. participates on the Scientific Advisory Board for Adaptimmune Limited, Axio Research, Celaid Therapeutics, FibroBiologics, Navan Technologies, New York Blood Center, and Zelluna Immunotherapy. The remaining authors declare no competing interests.
PubMed

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