Published in

OAE Publishing, Journal of Translational Genetics and Genomics, 4(7), p. 230-235, 2023

DOI: 10.20517/jtgg.2023.25

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

Journal article published in 2023 by Lara V. Graham, Jack G. Fisher ORCID, Salim I. Khakoo, Matthew D. Blunt ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.