Natural killer cells in antitumour adoptive cell immunotherapy.
Natural killer cells in antitumour adoptive cell immunotherapy.
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DOI：
10.1038/s41568-022-00491-0
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发表时间：
2022-10
期刊：
影响因子：
--
通讯作者：
Rezvani K
中科院分区：
文献类型：
--
作者：
Laskowski TJ;Biederstädt A;Rezvani K
自然杀伤（NK）细胞包括独特的先天淋巴样细胞群体，其被赋予识别和消除病毒感染细胞和肿瘤细胞的内在能力。NK细胞具有多种细胞毒性机制和通过细胞因子产生调节免疫应答的能力，在抗癌免疫中发挥关键作用。近二十年前，当NK细胞作为免疫抑制剂在治疗晚期白血病患者中显示出安全性和有效性时，这种作用就得到了阐明。近年来，随着嵌合抗原受体（CAR）工程过继性T细胞疗法的范式转变成功以及可以将细胞转化为强大的抗肿瘤武器的技术进步，对NK细胞作为免疫疗法候选者的兴趣呈指数级增长。开发基于NK细胞的疗法的策略侧重于通过共刺激信号传导、检查点抑制和细胞因子装甲来增强NK细胞的效力和持久性，并旨在通过CAR的表达或使用嵌合体分子将NK细胞特异性重定向至肿瘤。在临床上，第一代NK细胞疗法已经取得了可喜的成果，显示出令人鼓舞的疗效和显著的安全性，从而激发了持续创新的巨大热情。在这篇综述中，我们描述了增强NK细胞细胞毒性和寿命的各种方法，评估了挑战和机遇，并反思了从临床中吸取的经验教训将如何指导下一代NK细胞产品的设计，这些产品将解决每种癌症的独特复杂性。本文综述了自然杀伤（NK）细胞为基础的免疫疗法的概述。作者描述了用于增加NK细胞细胞毒性和持久性的各种工程策略，以及下一代NK细胞疗法未来设计的当前挑战和机遇。
Natural killer (NK) cells comprise a unique population of innate lymphoid cells endowed with intrinsic abilities to identify and eliminate virally infected cells and tumour cells. Possessing multiple cytotoxicity mechanisms and the ability to modulate the immune response through cytokine production, NK cells play a pivotal role in anticancer immunity. This role was elucidated nearly two decades ago, when NK cells, used as immunotherapeutic agents, showed safety and efficacy in the treatment of patients with advanced-stage leukaemia. In recent years, following the paradigm-shifting successes of chimeric antigen receptor (CAR)-engineered adoptive T cell therapy and the advancement in technologies that can turn cells into powerful antitumour weapons, the interest in NK cells as a candidate for immunotherapy has grown exponentially. Strategies for the development of NK cell-based therapies focus on enhancing NK cell potency and persistence through co-stimulatory signalling, checkpoint inhibition and cytokine armouring, and aim to redirect NK cell specificity to the tumour through expression of CAR or the use of engager molecules. In the clinic, the first generation of NK cell therapies have delivered promising results, showing encouraging efficacy and remarkable safety, thus driving great enthusiasm for continued innovation. In this Review, we describe the various approaches to augment NK cell cytotoxicity and longevity, evaluate challenges and opportunities, and reflect on how lessons learned from the clinic will guide the design of next-generation NK cell products that will address the unique complexities of each cancer. This review gives an overview of natural killer (NK) cell-based immunotherapies. The authors describe the various engineering strategies used to increase NK cell cytotoxicity and persistence, as well as the current challenges and opportunities for the future design of next-generation NK cell therapies.
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影响因子：
29
作者：
Cascone T;McKenzie JA;Mbofung RM;Punt S;Wang Z;Xu C;Williams LJ;Wang Z;Bristow CA;Carugo A;Peoples MD;Li L;Karpinets T;Huang L;Malu S;Creasy C;Leahey SE;Chen J;Chen Y;Pelicano H;Bernatchez C;Gopal YNV;Heffernan TP;Hu J;Wang J;Amaria RN;Garraway LA;Huang P;Yang P;Wistuba II;Woodman SE;Roszik J;Davis RE;Davies MA;Heymach JV;Hwu P;Peng W
通讯作者：
Peng W
影响因子：
8.7
作者：
Allard B;Longhi MS;Robson SC;Stagg J
通讯作者：
Stagg J
对供体记忆样的NK细胞的多维分析揭示了白血病的继发性免疫疗法后与反应的新关联。
影响因子：
28.2
作者：
Berrien-Elliott MM;Cashen AF;Cubitt CC;Neal CC;Wong P;Wagner JA;Foster M;Schappe T;Desai S;McClain E;Becker-Hapak M;Foltz JA;Cooper ML;Jaeger N;Srivatsan SN;Gao F;Romee R;Abboud CN;Uy GL;Westervelt P;Jacoby MA;Pusic I;Stockerl-Goldstein KE;Schroeder MA;DiPersio J;Fehniger TA
通讯作者：
Fehniger TA
影响因子：
64.5
作者：
André P;Denis C;Soulas C;Bourbon-Caillet C;Lopez J;Arnoux T;Bléry M;Bonnafous C;Gauthier L;Morel A;Rossi B;Remark R;Breso V;Bonnet E;Habif G;Guia S;Lalanne AI;Hoffmann C;Lantz O;Fayette J;Boyer-Chammard A;Zerbib R;Dodion P;Ghadially H;Jure-Kunkel M;Morel Y;Herbst R;Narni-Mancinelli E;Cohen RB;Vivier E
通讯作者：
Vivier E
影响因子：
20.3
作者：
Bryceson, YT;March, ME;Long, EO
通讯作者：
Long, EO