嵌合抗原受体T细胞（CAR-T）疗法极大地改变了癌症的治疗前景，细胞因子释放综合征（CRS）是病理性免疫系统激活的严重全身炎症反应，也是CAR-T治疗过程中最常见且致命的毒性反应。目前CRS机制尚未完全阐明，临床前研究的实验模型主要包括异种移植免疫缺陷小鼠模型、同源小鼠模型、转基因小鼠模型、人源化小鼠模型和非人灵长类动物模型。由于种属差异且缺乏体外细胞模型，临床前预测CAR-T细胞引起CRS的风险仍是亟待解决的问题。从CRS的相关指导原则及法规、机制及临床前安全性评价方法和模型3个方面对CAR-T诱发的CRS进行综述，以期为CAR-T细胞治疗产品的临床前安全性评价策略提供新的思路。

Chimeric antigen receptor T cell (CAR-T) therapy has greatly changed the prospects of cancer treatment. Cytokines release syndrome (CRS) is a severe systemic inflammatory response caused by pathological immune system activation, and is also the most common and lethal toxicity during CAR-T cell therapy. At present, the mechanism of CRS has not been fully clarified. Preclinical test models mainly include xenograft mouse model, syngeneic mouse model, transgenic mouse model, humanized mouse model and non-human primate animal model. Due to species differences and the lack of in vita cell models, preclinical prediction the risk of CAR-T cell causes CRS is still an urgent problem. This paper reviewed the relevant guidelines and regulations, mechanisms and preclinical safety evaluation methods and models of CRS in order to provide new ideas for preclinical safety evaluation strategies of CAR-T cell therapy products.

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