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CAR NK 细胞的临床格局

英文原题:The clinical landscape of CAR NK cells.

查看英文原题

The clinical landscape of CAR NK cells.

PubMed 2025/03/27(内容时间) Exp Hematol Oncol Q1 · IF 17.5(JCR 2025)

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中文摘要

CAR-NK 细胞疗法已成为 CAR-T 疗法的一种有前景替代方案,在安全性和通用性方面具有显著优势。本文探讨 CAR-NK 的当前临床格局、其在血液系统恶性肿瘤和实体瘤中的应用,以及治疗自身免疫性疾病的潜力。分析基于聚焦 CAR-NK 的 120 项临床试验数据,并介绍这些研究的人群构成和特征。本文进一步概述正在研究的具体靶点和疾病,以及所使用的主要细胞来源、基因修饰、联合治疗策略、预处理和剂量方案及制备策略。16 项临床试验的初步结果显示 CAR-NK 疗效有希望,尤其是在 B 细胞恶性肿瘤中,其缓解率可与 CAR-T 相当,同时细胞因子释放综合征(CRS)、免疫效应细胞相关神经毒性综合征(ICANS)和移植物抗宿主病(GvHD)等重度不良反应发生率较低。

然而,实体瘤应用仍面临挑战,迄今观察到的疗效仅为中等。分析显示,研究日益聚焦于增强 CAR-NK 持久性、扩大治疗靶点范围,以及改进制备流程以提高可及性和规模化能力。随着 NK 细胞工程不断进步及临床应用增加,CAR-NK 预计将成为下一代免疫疗法的重要组成部分,不仅用于癌症治疗,也可能用于免疫介导性疾病。

展开英文摘要原文

Chimeric antigen receptor (CAR) NK cell therapy has emerged as a promising alternative to CAR T cell therapy, offering significant advantages in terms of safety and versatility.

Here we explore the current clinical landscape of CAR NK cells, and their application in hematologic malignancies and solid cancers, as well as their potential for treating autoimmune disorders.

Our analysis draws from data collected from 120 clinical trials focused on CAR NK cells, and presents insights into the demographics and characteristics of these studies.

We further outline the specific targets and diseases under investigation, along with the major cell sources, genetic modifications, combination strategies, preconditioning- and dosing regimens, and manufacturing strategies being utilized.

Initial results from 16 of these clinical trials demonstrate promising efficacy of CAR NK cells, particularly in B cell malignancies, where response rates are comparable to those seen with CAR T cells but with lower rates of severe adverse effects, such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and graft-versus-host disease (GvHD).

However, challenges remain in solid tumor applications, where only modest efficacy has been observed to date.

Our analysis reveals that research is increasingly focused on enhancing CAR NK cell persistence, broadening their therapeutic targets, and refining manufacturing processes to improve accessibility and scalability. With recent advancements in NK cell engineering and their increased clinical applications, CAR NK cells are predicted to become an integral component of next-generation immunotherapies, not only for cancer but potentially for immune-mediated diseases as well.

论文信息

作者
Jørgensen LV、Christensen EB、Barnkob MB、Barington T
第一作者单位
Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.Denmark
通讯作者单位
Department of Clinical Immunology, Odense University Hospital, Odense, Denmark. torben.barington@rsyd.dk.Denmark
文献类型
综述
期刊
Experimental hematology & oncology2025 Mar 27
原文标识
PubMed 40149002 · DOI 10.1186/s40164-025-00633-8