文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

将杀伤细胞免疫球蛋白样受体(KIR)作为改善嵌合抗原受体自然杀伤细胞(CAR-NK)功能的新方法。

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

作者信息

Graham Lara V, Fisher Jack G, Khakoo Salim I, Blunt Matthew D

机构信息

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

出版信息

J Transl Genet Genom. 2023 Dec 5;7:230-235. doi: 10.20517/jtgg.2023.25.


DOI:10.20517/jtgg.2023.25
PMID:38229912
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7615527/
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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa8e/7615527/5398badd8662/EMS192612-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa8e/7615527/5398badd8662/EMS192612-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa8e/7615527/5398badd8662/EMS192612-f001.jpg

相似文献

[1]
Targeting KIR as a novel approach to improve CAR-NK cell function.

J Transl Genet Genom. 2023-12-5

[2]
KIR-based inhibitory CARs overcome CAR-NK cell trogocytosis-mediated fratricide and tumor escape.

Nat Med. 2022-10

[3]
Intrinsic Functional Potential of NK-Cell Subsets Constrains Retargeting Driven by Chimeric Antigen Receptors.

Cancer Immunol Res. 2018-2-19

[4]
Outsmarting trogocytosis to boost CAR NK/T cell therapy.

Mol Cancer. 2023-11-16

[5]
Peptide: MHC-based DNA vaccination strategy to activate natural killer cells by targeting killer cell immunoglobulin-like receptors.

J Immunother Cancer. 2021-5

[6]
Impact of killer-immunoglobulin-like receptor and human leukocyte antigen genotypes on the efficacy of immunotherapy in acute myeloid leukemia.

Leukemia. 2017-12

[7]
Hierarchy of the human natural killer cell response is determined by class and quantity of inhibitory receptors for self-HLA-B and HLA-C ligands.

J Immunol. 2007-11-1

[8]
Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire and Are Associated With Vpu Sequence Variations Impacting Downmodulation of HLA-C.

Front Immunol. 2022

[9]
CAR-NK Cells: From Natural Basis to Design for Kill.

Front Immunol. 2021

[10]
Impact of KIR-HLA Genotype on Natural-Killer-Cell-Based Immunotherapy for Preventing Hepatocellular Carcinoma after Living-Donor Liver Transplantation.

Cancers (Basel). 2024-1-26

引用本文的文献

[1]
Emerging roles of KIR2DL4 in cancer immunotherapy.

Breast Cancer. 2025-6-23

[2]
The Role of Killer Ig-like Receptors in Diseases from A to Z.

Int J Mol Sci. 2025-3-31

[3]
The Effects of Cancer Immunotherapy on Fertility: Focus on Hematological Malignancies.

Biomedicines. 2024-9-15

本文引用的文献

[1]
Natural Killer Cell Engagers (NKCEs): a new frontier in cancer immunotherapy.

Front Immunol. 2023

[2]
Rational design of PD-1-CD28 immunostimulatory fusion proteins for CAR T cell therapy.

Br J Cancer. 2023-9

[3]
Cytokines induced memory-like NK cells engineered to express CD19 CAR exhibit enhanced responses against B cell malignancies.

Front Immunol. 2023

[4]
Allogeneic natural killer cell therapy.

Blood. 2023-2-23

[5]
KIR-based inhibitory CARs overcome CAR-NK cell trogocytosis-mediated fratricide and tumor escape.

Nat Med. 2022-10

[6]
KIR2DS2 Expression Identifies NK Cells With Enhanced Anticancer Activity.

J Immunol. 2022-7-15

[7]
Low-affinity CAR T cells exhibit reduced trogocytosis, preventing rapid antigen loss, and increasing CAR T cell expansion.

Leukemia. 2022-7

[8]
Targeting human leukocyte antigen G with chimeric antigen receptors of natural killer cells convert immunosuppression to ablate solid tumors.

J Immunother Cancer. 2021-10

[9]
The Role of Trogocytosis in the Modulation of Immune Cell Functions.

Cells. 2021-5-19

[10]
Peptide: MHC-based DNA vaccination strategy to activate natural killer cells by targeting killer cell immunoglobulin-like receptors.

J Immunother Cancer. 2021-5

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索