单克隆抗体引起细胞因子释放综合征的机制及临床前评价进展  

Mechanism and preclinical evaluation of cytokine release syndrome induced by monoclonal antibodies

作　　者：傅盈双 李双星 姜华[1] 林志[1] FU Ying-shuang;LI Shuang-xing;JIANG Hua;LIN Zhi(National Center for Safety Evaluation of Drugs,Beijing Key Laboratory for Nonclinical Safety Evaluation of Drugs,National Institutes for Food and Drug Control,Beijing 100176,China)

机构地区：[1]国家药物安全评价监测中心药物非临床安全性评价研究北京市重点实验室/中国食品药品检定研究院,北京100176

出　　处：《中国新药杂志》2024年第14期1442-1448,共7页Chinese Journal of New Drugs

摘　　要：单克隆抗体药物(简称单抗药物)在癌症、免疫相关疾病等方面治疗前景广阔。随着临床前及临床研究数据的积累,人们对其免疫毒性的认识越来越深入。细胞因子释放综合征(cytokines release syndrome, CRS)是一种由多种因素诱导的免疫系统广泛激活的全身炎症反应,单抗药物可通过激活效应细胞或非效应细胞引起细胞因子释放,严重威胁患者的健康。临床前主要通过体外细胞因子释放实验(cytokine release assay, CRA)及体内试验综合评估单抗药物的安全性。虽然体内和体外实验的数据可以相互补充,但通常不能完全预测临床发生,临床前预测单抗药物引起CRS的风险仍是一个亟待解决的问题。本文将从CRS的发生机制、相关法规及临床前评价方法3个方面对单抗治疗产品诱发的CRS进行综述,以期为单抗治疗产品的临床前安全性评价策略提供新的思路。Monoclonal antibody drugs have broad therapeutic prospects in cancer,immune-related diseases,and other fields.With the accumulation of preclinical and clinical research data,people's understanding of their immunotoxicity has become deeper and deeper.Cytokine release syndrome(CRS)is a systemic inflammatory reaction that immune system is widely activated by various factors.Monoclonal antibodies can cause cytokine release by activating effector cells or non-effector cells,which seriously threatens the health of patients.Before clinical trials,the safety of monoclonal antibodies is evaluated by in vitro CRA and in vivo test.Although data from in vivo and in vitro tests can complement each other,clinical occurrence is usually not fully predicted,and preclinical prediction of the risk of CRS induced by monoclonal antibodies remains an issue to be solved.This paper reviewed the cytokine release syndrome induced by monoclonal antibody products from three aspects,including mechanisms,relevant regulations and preclinical evaluation methods of CRS,in order to provide new ideas for the preclinical safety evaluation strategies of monoclonal antibody products.

关 键 词：细胞因子释放综合征 单克隆抗体药物 机制 安全性评价 细胞因子释放实验 

分 类 号：R979.5[医药卫生—药品]