Saleki Kiarash, Mohamadi Mohamad Hosein, Alijanizadeh Parsa, Rezaei Nima
Student Research Committee, Babol University of Medical Sciences, Babol, Iran.
USERN Office, Babol University of Medical Sciences, Babol, Iran.
Expert Rev Clin Immunol. 2023 Jul-Dec;19(11):1361-1383. doi: 10.1080/1744666X.2023.2248390. Epub 2023 Sep 4.
Chimeric antigen receptor (CAR) T-cell is among the most prevalent approaches that act by directing T-cells toward cancer; however, they need to be optimized to minimize side effects and maximize efficacy before being used as standard treatment for malignancies. Neurotoxicity associated with CAR T-cell therapy has been well-documented in recent works.
In this regard, two established syndromes exist. Immune effector cell-associated neurotoxicity syndrome (ICANS), previously called cytokine release encephalopathy syndrome (CRES), is a neuropsychiatric condition which can occur after therapy by immune effector cells (IEC) and T-lymphocytes utilizing treatments. Another syndrome is cytokine release syndrome (CRS), which may overlap with ICANS.
ICANS clinical manifestations include cerebral edema, mild lethargy, aphasia, and seizures. Notably, ICANS is associated with changes to EEG and neuroradiological findings. Therefore, it is necessary to make a timely and accurate diagnosis of neurological complications of CAR T-cells by clinical presentations, neuroimaging, and EEG. Since neurological events by different CAR T-cell products are heterogeneous, guides should be developed according to each product. Here, we provide an updated review of general information on CAR T-cell therapies and applications, neurological syndromes associated with their use, and risk factors contributing to ICANS.
嵌合抗原受体(CAR)T细胞是引导T细胞靶向癌症的最常用方法之一;然而,在用作恶性肿瘤的标准治疗方法之前,需要对其进行优化,以尽量减少副作用并最大化疗效。近期研究已充分证明了与CAR T细胞疗法相关的神经毒性。
在这方面,存在两种已确定的综合征。免疫效应细胞相关神经毒性综合征(ICANS),以前称为细胞因子释放脑病综合征(CRES),是一种神经精神疾病,可在免疫效应细胞(IEC)和T淋巴细胞治疗后发生。另一种综合征是细胞因子释放综合征(CRS),它可能与ICANS重叠。
ICANS的临床表现包括脑水肿、轻度嗜睡、失语和癫痫发作。值得注意的是,ICANS与脑电图和神经影像学检查结果的变化有关。因此,有必要通过临床表现、神经影像学和脑电图对CAR T细胞的神经并发症进行及时准确的诊断。由于不同CAR T细胞产品引起的神经事件具有异质性,应根据每种产品制定指导原则。在此,我们提供了关于CAR T细胞疗法及应用的一般信息、与其使用相关的神经综合征以及导致ICANS的危险因素的最新综述。