嵌合抗原受体-T细胞治疗产品临床前评价模型研究进展  

Research progress on preclinical evaluation models of CAR-T cell therapy products

作　　者：李双星 霍桂桃[1] 屈哲[1] 杨艳伟[1] 张頔[1] 林志[1] LI Shuangxing;HUO Guitao;QU Zhe;YANG Yanwei;ZHANG Di;LIN Zhi(National Center for Safety Evaluation of Drugs,National Institutes for Food and Drug Control,Beijing 100176,China)

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

出　　处：《药物评价研究》2024年第8期1669-1677,共9页Drug Evaluation Research

摘　　要：癌症的治疗一直被视为医学上最大的挑战,近年来,随着多种嵌合抗原受体-T细胞(CAR-T)治疗产品的获批上市,为攻克癌症带来了新的希望。然而,在临床应用中,CAR-T细胞治疗产品均存在一定的不良反应,这提示CAR-T细胞治疗产品的临床前评价模型十分重要。目前,CAR-T细胞治疗产品的临床前评价模型主要包括体内评价模型和体外评价模型,其中体内评价模型包括同源移植小鼠模型、基因工程小鼠模型、人源化小鼠模型、人源肿瘤异体移植模型及非人灵长类动物模型;体外评价模型包括肿瘤类器官模型、器官芯片模型与人工智能预测模型。对各种评价模型的进展及优缺点进行综述,以期为CAR-T细胞治疗产品的临床前评价提供参考。The treatment of cancer has always been regarded as the biggest challenge in medicine.In recent years,with the approval and launch of various chimeric antigen receptor T cell therapy(CAR-T)products,new hope has been brought to the research of overcoming cancer.However,in clinical practice,CAR-T cell therapy products have certain adverse reactions,which suggests that preclinical evaluation models of CAR-T cell therapy products is crucial.At present,the preclinical evaluation methods for CAR-T cell therapy products mainly include in vivo evaluation models and in vitro evaluation models.In vivo evaluation models include syngeneic mouse model,genetically engineered mouse models,humanized mouse models,patient-derived tumor xenograft models and non-human primate models.In vitro evaluation models include patients derived organoids models,human-on-a-chip models and artificial intelligence prediction.This article aims to review the progress and advantages and disadvantages of various evaluation methods to lay a theoretical and research foundation for preclinical evaluation of CAR-T cell therapy products.

关 键 词：嵌合抗原受体T细胞 临床前评价 体内评价模型 体外评价模型 癌症 

分 类 号：R965.1[医药卫生—药理学]