Targeting KIR as a novel approach to improve CAR-NK cell function
Targeting KIR as a novel approach to improve CAR-NK cell function
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.
CAR-NK cells, chimeric antigen receptor (CAR), immunotherapy, Killer immunoglobulin-like receptors (KIRs), natural killer cells (NK cells)
230-235
Graham, Lara V.
4a7bbe46-4e8e-476d-87f5-5c83304a5293
Fisher, Jack G.
5d9176a9-c6a6-4234-a178-3054eee07eb4
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Blunt, Matthew D.
b1109de3-6045-4bc3-bd77-6cf26504697d
5 December 2023
Graham, Lara V.
4a7bbe46-4e8e-476d-87f5-5c83304a5293
Fisher, Jack G.
5d9176a9-c6a6-4234-a178-3054eee07eb4
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Blunt, Matthew D.
b1109de3-6045-4bc3-bd77-6cf26504697d
Graham, Lara V., Fisher, Jack G., Khakoo, Salim I. and Blunt, Matthew D.
(2023)
Targeting KIR as a novel approach to improve CAR-NK cell function.
Journal of Translational Genetics and Genomics, 7 (4), .
(doi:10.20517/jtgg.2023.25).
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.
Text
jtgg7025
- Version of Record
More information
Accepted/In Press date: 30 November 2023
e-pub ahead of print date: 5 December 2023
Published date: 5 December 2023
Additional Information:
Funding Information:
This work was supported by a grant from the Medical Research Council (MR/M019829/1 to S.I.K), a John Goldman Fellowship from Leukaemia UK, funding from the Medical Research Council (DTP award MR/N014308/1), the Cancer Immunology Fund (University of Southampton) and Cancer Research UK (ECRIN-M3 accelerator award C42023/A29370).
Publisher Copyright:
© The Author(s) 2023.
Keywords:
CAR-NK cells, chimeric antigen receptor (CAR), immunotherapy, Killer immunoglobulin-like receptors (KIRs), natural killer cells (NK cells)
Identifiers
Local EPrints ID: 486269
URI: http://eprints.soton.ac.uk/id/eprint/486269
ISSN: 2578-5281
PURE UUID: 5ff1b7d9-a3c7-4352-b612-471fa6f66eda
Catalogue record
Date deposited: 16 Jan 2024 17:40
Last modified: 18 Mar 2024 03:59
Export record
Altmetrics
Contributors
Author:
Lara V. Graham
Author:
Jack G. Fisher
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics