Mechanisms of immune effector cell-associated neurotoxicity syndrome after CAR-T treatment.

IF 4.6 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Tianning Gu, Kejia Hu, Xiaohui Si, Yongxian Hu, He Huang
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引用次数: 2

Abstract

Chimeric antigen receptor T-cell (CAR-T) treatment has revolutionized the landscape of cancer therapy with significant efficacy on hematologic malignancy, especially in relapsed and refractory B cell malignancies. However, unexpected serious toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) still hamper its broad application. Clinical trials using CAR-T cells targeting specific antigens on tumor cell surface have provided valuable information about the characteristics of ICANS. With unclear mechanism of ICANS after CAR-T treatment, unremitting efforts have been devoted to further exploration. Clinical findings from patients with ICANS strongly indicated existence of overactivated peripheral immune response followed by endothelial activation-induced blood-brain barrier (BBB) dysfunction, which triggers subsequent central nervous system (CNS) inflammation and neurotoxicity. Several animal models have been built but failed to fully replicate the whole spectrum of ICANS in human. Hopefully, novel and powerful technologies like single-cell analysis may help decipher the precise cellular response within CNS from a different perspective when ICANS happens. Moreover, multidisciplinary cooperation among the subjects of immunology, hematology, and neurology will facilitate better understanding about the complex immune interaction between the peripheral, protective barriers, and CNS in ICANS. This review elaborates recent findings about ICANS after CAR-T treatment from bed to bench, and discusses the potential cellular and molecular mechanisms that may promote effective management in the future. This article is categorized under: Cancer > Biomedical Engineering Immune System Diseases > Molecular and Cellular Physiology Neurological Diseases > Molecular and Cellular Physiology.

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CAR-T治疗后免疫效应细胞相关神经毒性综合征的机制。
嵌合抗原受体t细胞(CAR-T)治疗已经彻底改变了癌症治疗的前景,对血液恶性肿瘤,特别是复发和难治性B细胞恶性肿瘤有显著的疗效。然而,细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)等意想不到的严重毒性仍阻碍其广泛应用。利用CAR-T细胞靶向肿瘤细胞表面特异性抗原的临床试验提供了有关ICANS特征的宝贵信息。CAR-T治疗后ICANS的机制尚不清楚,人们一直在不懈地探索。来自ICANS患者的临床结果强烈表明存在过度激活的外周免疫反应,随后内皮激活诱导的血脑屏障(BBB)功能障碍,从而引发随后的中枢神经系统(CNS)炎症和神经毒性。已经建立了一些动物模型,但未能在人类中完全复制ICANS的整个范围。希望像单细胞分析这样新颖而强大的技术可以从不同的角度帮助破译ICANS发生时中枢神经系统内的精确细胞反应。此外,免疫学、血液学和神经学学科之间的多学科合作将有助于更好地了解ICANS中外周、保护性屏障和中枢神经系统之间复杂的免疫相互作用。这篇综述阐述了CAR-T治疗后ICANS的最新发现,并讨论了可能促进未来有效治疗的潜在细胞和分子机制。本文分类如下:癌症>生物医学工程免疫系统疾病>分子与细胞生理学神经疾病>分子与细胞生理学。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
WIREs Mechanisms of Disease
WIREs Mechanisms of Disease MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
11.40
自引率
0.00%
发文量
45
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