嵌合抗原受体T细胞免疫疗法相关神经毒性研究进展

Research progress on neurotoxicity related to chimeric antigen receptor T cell immunotherapy

免疫效应细胞相关神经毒性综合征(ICANS)是嵌合抗原受体T细胞(CAR-T)免疫疗法常见的不良反应,其发生机制主要与大脑壁细胞破坏、细胞因子水平升高、自然杀伤细胞介导的炎症作用以及内皮细胞激活有关。ICANS的临床表现主要为失语、震颤、书写困难、嗜睡、癫痫,严重者可出现窒息、昏迷或脑水肿,甚至危及生命。影响ICANS的因素包括年龄、CAR-T的扩增峰值、产品种类和疾病类型等。美国血液与骨髓移植学会推荐对轻度ICANS患者给予对症支持治疗,严重者可以采用激素冲击治疗。

Immune effector cell‐associated neurotoxicity syndrome(ICANS)is a common adverse reaction of chimeric antigen receptor T‐cell(CAR‐T)immunotherapy.Its mechanism is mainly related to the destruction of brain mural cells,increase of cytokine level,the inflammation mediated by natural killer cells,and the activation of endothelial cells.The main clinical manifestations of ICANS are aphasia,tremor,dysgraphia,drowsiness,and epilepsy.In severe cases,asphyxia,coma,or brain edema may occur,and some‐times it is even life‐threatening.The factors affecting ICANS include age,peak value of CAR‐T amplifica‐tion,product type,and disease type,etc.American Society for Blood and Marrow Transplantation recom‐mends symptomatic and supportive treatments for mild ICANS and hormonal shock therapy for severe cases.