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CAR-T 细胞治疗在神经病学中的当前与未来作用:综述

英文原题:Current and Future Roles of Chimeric Antigen Receptor T-Cell Therapy in Neurology: A Review.

查看英文原题

Current and Future Roles of Chimeric Antigen Receptor T-Cell Therapy in Neurology: A Review.

PubMed 2025/01/01(内容时间) JAMA Neurol Q1 · IF 23.6(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

研究概要

CAR-T 细胞预示着神经系统疾病治疗格局的新时代。

中文摘要

重要性:分子工程进步促进了表达合成受体的工程化T细胞开发,这类受体称为嵌合抗原受体(CAR)。该技术不仅有望用于癌症治疗,也可能应对多种其他疾病。本综述全面概述CAR-T 细胞疗法在神经病学领域的当前应用及未来潜力,尤其关注原发性脑肿瘤和自身免疫性神经系统疾病。 观察结果:CAR-T 细胞治疗胶质母细胞瘤具有潜力,但首次人体试验未取得显著成功,或仅在部分患者中获得有限疗效。迄今CAR-T 细胞疗法治疗多发性硬化症的疗效已在动物模型中得到证明,但仍需更大规模的人体研究加以确认。CAR-T 细胞已显示出治疗复发/难治性水通道蛋白4免疫球蛋白G血清阳性视神经脊髓炎谱系疾病患者的疗效。仍需更多患者参与的研究确认这些结果。CAR-T 细胞治疗全身型重症肌无力的病例也报告了成功。嵌合自身抗体受体T细胞是一种改造型CAR-T 细胞,可靶向分泌自身抗体的自身反应性B细胞;研究者已在体外和体内选择性靶向自身反应性抗N-甲基-D-天冬氨酸受体B细胞,为人体研究以及拓展至其他伴神经元或胶质细胞抗体的自身免疫性脑炎奠定基础。 结论与意义:CAR-T 细胞开启了神经系统疾病治疗的新阶段。其用于胶质母细胞瘤等实体瘤尚未普遍取得强效疗效,但新兴创新策略展现出潜力;对于某些自身免疫性神经系统疾病,其治疗效果值得期待。

展开英文摘要原文

Advancements in molecular engineering have facilitated the creation of engineered T cells that express synthetic receptors, termed chimeric antigen receptors (CARs). This is promising not only in cancer treatment but also in addressing a spectrum of other conditions. This review provides a comprehensive overview of the current approaches and future potential of CAR T-cell therapy in the field of neurology, particularly for primary brain tumors and autoimmune neurological disorders. OBSERVATIONS: CAR T-cell therapy for glioblastoma is promising; however, first-in-human trials did not yield significant success or showed only limited success in a subset of patients. To date, the efficacy of CAR T-cell therapies has been demonstrated in animal models of multiple sclerosis, but larger human studies to corroborate the efficacy remain pending. CAR T cells showed efficacy in treatment of patients with relapsed or refractory aquaporin 4-immunoglobulin G-seropositive neuromyelitis optica spectrum disorders. Further studies with larger patient populations are needed to confirm these results. Success was reported also for treatment of cases with generalized myasthenia gravis using CAR T cells. Chimeric autoantibody receptor T cells, representing a modified form of CAR T cells directed against autoreactive B cells secreting autoantibodies, were used to selectively target autoreactive anti-N-methyl-d-aspartate B cells under in vitro and in vivo conditions, providing the basis for human studies and application to other types of autoimmune encephalitis associated with neuronal or glial antibodies.

CAR T cells herald a new era in the therapeutic landscape of neurological disorders. While their application in solid tumors, such as glioblastoma, has not universally yielded robust success, emerging innovative strategies show promise, and there is optimism for their effectiveness in certain autoimmune neurological disorders.

论文信息

作者
Ismail FS、Gallus M、Meuth SG、Okada H、Hartung HP、Melzer N
第一作者单位
Department of Neurology, Klinikum Vest, Academic Teaching Hospital of the Ruhr University Bochum, Recklinghausen, Germany.Germany
通讯作者单位
Department of Neurology, Medical Faculty and University Hospital, Heinrich-Heine University of Düsseldorf, Düsseldorf, Germany.Germany
文献类型
综述
期刊
JAMA neurology2025 Jan 1
原文标识
PubMed 39585688 · DOI 10.1001/jamaneurol.2024.3818