嵌合抗原受体T细胞产品非临床免疫毒性评价思考

doi:10.19803/j.1672-8629.20230134

中国药物警戒 ›› 2024, Vol. 21 ›› Issue (9): 1051-1055.
DOI: 10.19803/j.1672-8629.20230134

嵌合抗原受体T细胞产品非临床免疫毒性评价思考

刘畅, 施畅, 尹纪业^*

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

收稿日期:2024-03-09 出版日期:2024-09-15 发布日期:2024-09-14
通讯作者: ^*尹纪业,男,博士,研究员,药物毒性评价。E-mail：yinjiye11@163.com
作者简介:刘畅,女,硕士,助理实验师,药理毒理。
基金资助:
国家科技重大专项重大新药创制（2018ZX0971-1003-007）

Nonclinical immunotoxicity evaluation of CAR-T cell products

LIU Chang, SHI Chang, YIN Jiye^*

State Key Laboratory of National Security Specially Needed Medicines, Academy of Military Medical Sciences, National Beijing Center for Drug Safety Evaluation and Research, Beijing 100850, China

Received:2024-03-09 Online:2024-09-15 Published:2024-09-14

摘要/Abstract

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。

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

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.

Key words: chimeric antigen receptor T, immunotoxicity, cytokine release syndrome, integrated strategy, animal models, T cell dependent antibody response

中图分类号:

R994.1

刘畅, 施畅, 尹纪业. 嵌合抗原受体T细胞产品非临床免疫毒性评价思考[J]. 中国药物警戒, 2024, 21(9): 1051-1055.

LIU Chang, SHI Chang, YIN Jiye. Nonclinical immunotoxicity evaluation of CAR-T cell products[J]. Chinese Journal of Pharmacovigilance, 2024, 21(9): 1051-1055.

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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

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