Graham Lara V, Fisher Jack G, Khakoo Salim I, Blunt Matthew D
School of Clinical and Experimental Sciences, University of Southampton, Southampton SO16 6YD, UK.
J Transl Genet Genom. 2023 Dec 5;7:230-235. doi: 10.20517/jtgg.2023.25.
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.
嵌合抗原受体(CAR)自然杀伤(NK)细胞在临床试验中显示出有前景的活性,并且与CAR-T细胞相比具有良好的安全性。杀伤细胞免疫球蛋白样受体(KIR)在控制NK细胞功能中起关键作用,最近,这个激活和抑制性受体家族已成为改善CAR-NK功能的靶点。这些策略包括利用抑制性KIR减少与吞噬相关的NK细胞自相残杀,下调CAR-NK细胞上的抑制性KIR以减轻HLA介导的抑制,选择富含激活性KIR的CAR-NK细胞供体,以及在新型CAR构建体中使用激活性KIR胞内结构域。这些临床前研究证明了靶向KIR以提高CAR-NK细胞疗效和患者预后的潜在效用。
J Transl Genet Genom. 2023-12-5
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