Targeting KIR as a novel approach to improve CAR-NK cell function.

J Transl Genet Genom

School of Clinical and Experimental Sciences, University of Southampton, Southampton SO16 6YD, UK.

Published: December 2023


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Article Abstract

Chimeric antigen receptor (CAR) NK cells are demonstrating promising activity in clinical trials and possess a favorable safety profile compared to CAR-T cells. The Killer cell Immunoglobulin-like Receptors (KIR) have a critical role in the control of NK cell function, and recently, this family of activating and inhibitory receptors have been targeted to improve CAR-NK function. These strategies include the utilisation of inhibitory KIR to reduce trogocytosis-associated NK cell fratricide, the downregulation of inhibitory KIR on CAR-NK cells to alleviate HLA mediated suppression, the selection of CAR-NK cell donors enriched for activating KIR, and the use of activating KIR intracellular domains within novel CAR constructs. These pre-clinical studies demonstrate the potential utility of targeting the KIR to improve CAR-NK cell efficacy and patient outcomes.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615527PMC
http://dx.doi.org/10.20517/jtgg.2023.25DOI Listing

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