嵌合抗原受体T细胞产品非临床免疫毒性评价思考
Nonclinical immunotoxicity evaluation of CAR-T cell products
刘畅 1施畅 1尹纪业1
作者信息
- 1. 军事医学研究院国家安全特需药品全国重点实验室,国家北京药物安全评价研究中心,北京 100850
- 折叠
摘要
目的 分析嵌合抗原受体T(CAR-T)细胞产品非临床免疫毒性,为临床安全使用提供参考.方法 通过介绍CAR-T目前的研究现状,针对其产品的原理、特性和研究方向,以及CAR-T的免疫相关毒性,结合目前现有的指导原则以及免疫毒性试验进行总结和探讨.结果 目前针对不同类型的CAR-T免疫毒性评价方面相关指导原则的内容非常有限.通常是将免疫毒性试验整合到标准毒性实验中去进行初筛,再根据结果选择相应的免疫功能性实验作为附加实验.T细胞依赖性抗体应答(TDAR)是目前较为合适的用于整体评价CAR-T免疫毒性的方法.结论 目前尚没有完善的评价策略对CAR-T细胞产品进行免疫毒性评价.
Abstract
Objective Analysis of nonclinical immunotoxicity of CAT-T cell products,in order to provide a reference for safe clinical use.Methods The current research on CAR-T was outlined.The principles,characteristics,priorities of research,and immune-related toxicity of CAR-T products were analyzed based on related guidelines and immunotoxicity tests.Results The guidelines for evaluating the immunotoxicity of different types of CAR-T were inadequate.Currently,immunotoxicity tests were usually integrated into standard toxicity tests for initial screening before corresponding immune functional tests were selected as additional tests based on the results.TDAR was a preferable method for the overall evaluation of CAR-T immune toxicity.Conclusion There is a lack of appropriate evaluation strategies for the immunotoxicity evaluation of CAR-T cell products.
关键词
嵌合抗原受体T/免疫毒性/细胞因子释放综合征/组合策略/动物模型/T细胞依赖性抗体应答Key words
chimeric antigen receptor T/immunotoxicity/cytokine release syndrome/integrated strategy/animal models/T cell dependent antibody response引用本文复制引用
基金项目
国家科技重大专项重大新药创制(2018ZX0971-1003-007)
出版年
2024
NETL
NSTL
万方数据