细胞因子与嵌合抗原受体修饰T细胞免疫疗法不良反应的相关性及其靶向药物干预  

Relationship of cytokines to adverse reaction of chimeric antigen receptor T cell immunotherapy and targeted drug intervention

作　　者：张国林 景荣先[2] 邢以文 薛满 ZHANG Guolin;JING Rongxian;XING Yiwen;XUE Man(Suzhou Institute for Drug Control,Suzhou 215000,Jiangsu Province,China)

机构地区：[1]苏州市药品检验检测研究中心,江苏苏州215000 [2]苏州市立医院药学部,江苏苏州215000

出　　处：《中国生物制品学杂志》2023年第4期506-512,共7页Chinese Journal of Biologicals

摘　　要：嵌合抗原受体修饰T细胞(chimeric antigen receptor T cell,CAR-T)免疫治疗是目前最有潜力的恶性肿瘤过继性免疫疗法,具有不需要抗原递呈细胞(antigen presenting cell,APC)、不受主要组织相容性复合体(major histocompatibility complex,MHC)限制的优点。CAR-T免疫疗法除直接识别并杀灭肿瘤细胞外,还可形成记忆T细胞并建立长效的抗肿瘤机制。CAR-T免疫疗法治疗白血病、多发性骨髓瘤等非实体肿瘤的效果已得到广泛证实,在治疗实体肿瘤中也有巨大潜力。但CAR-T免疫疗法治疗过程中也会产生多种不良反应,如细胞因子释放综合征(cytokine release syndrome,CRS,也称细胞因子风暴)、神经系统毒性(neurotoxicity,NT)、脱靶效应等,其中CRS和NT的发生可能与治疗时细胞因子水平的异常变化有关。细胞因子水平剧烈升高是CRS的主要特征,细胞因子升高并非CAR-T疗法不良反应的根本原因,也并非不良反应的全部结果表现。CAR-T免疫疗法不良反应发生率高,甚至可能危及患者生命,而托珠单抗、阿那白滞素等细胞因子靶向药物可降低不良反应的发生率,改善患者的预后。本文对细胞因子与CAR-T免疫治疗并发CRS及NT的相关性以及细胞因子靶向药物的作用作一综述,以期为CAR-T免疫疗法的基础研究、质量控制及临床应用提供参考。Chimeric antigen receptor T cell(CAR-T)immunotherapy is the most potential adoptive immunotherapy for malignant tumors,which needs no antigen presenting cells(APC)and is not limited by major histocompatibiliy complex(MHC).CAR-T immunotherapy not only recognizes and kills tumor cells directly,but also forms memory T cells and establishs long-term anti-tumor mechanism,of which the effect in leukemia,multiple myeloma and other non-solid tumors as well as the great potential in solid tumors have been widely verified.However,a variety of adverse reactions such as cytokine release syndrome(CRS),neurotoxicity(NT)and miss target effect are produced during CAR-T immunotherapy,of which the occurrence of CRS and NT may be related to the abnormal level of cytokines.Remarkable increase of cytokine level is a major characteristics of CRS.However,the increase of cytokines is neither the root cause nor the only result of CAR-T adverse reaction.CAR-T immunotherapy has a high incidence of adverse reaction which may even endanger the life of patients.Cytokine targeted drugs such as Anakinra and Tocilizumab may decrease the incidence of adverse reaction and improve the prognosis of patients.This paper reviews the correlation of cytokines with CRS and NT in CAR-T immunotherapy and the effect of cytokine targeting drugs,so as to provide a reference for the basic research,quality control and clinical application of CAR-T immunotherapy.

关 键 词：嵌合抗原受体修饰T细胞 记忆T细胞 细胞因子释放综合征 神经系统毒性 细胞因子 托珠单抗 

分 类 号：R730.51[医药卫生—肿瘤]