文章摘要
黄瑛,侯田田,霍艳.CAR-T细胞治疗产品非临床研究动物模型的发展和应用概述[J].中国药事,2018,32(7):886-892
CAR-T细胞治疗产品非临床研究动物模型的发展和应用概述
Overview of the Development and Application of Animal Models in Non-clinical Studies of CAR-T Cell Therapy Products
投稿时间:2018-06-20  
DOI:10.16153/j.1002-7777.2018.07.007
中文关键词: 嵌合抗原受体T细胞  动物模型  非临床研究  有效性  安全性评价  毒性
英文关键词: CAR-T  animal models  non-clinical study  effectiveness  safety evaluation  toxicity
基金项目:十二五国家科技重大专项“生物大分子药物特殊评价关键技术研究”(编号2015ZX09501007-004)
作者单位E-mail
黄瑛 中国食品药品检定研究院, 药物非临床安全评价研究北京市重点实验室, 北京 100176  
侯田田 中国食品药品检定研究院, 药物非临床安全评价研究北京市重点实验室, 北京 100176  
霍艳 中国食品药品检定研究院, 药物非临床安全评价研究北京市重点实验室, 北京 100176 yanhuo@nifdc.org.cn 
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中文摘要:
      嵌合抗原受体T细胞(CAR-T,Chimeric Antigen Receptor T Cell)已成为近年来癌症免疫疗法领域的研究热点,由于其具有特异性高、选择性强等优点,在肿瘤治疗领域中具有巨大的潜力。同时,CAR-T疗法可能带来特殊毒性风险,包括细胞因子释放综合征、神经毒性、B细胞减少和靶向与脱靶毒性等。尽量在研发早期、在人体使用前获得CAR-T产品的有效性和安全性等非临床信息至关重要,选择合适的动物模型进行上述相关研究可以大大提高对临床结果的预测性。目前,已用于CAR-T产品研究和正处于探索阶段的动物模型主要包括同源小鼠模型、转基因小鼠、移植瘤小鼠模型、免疫系统重建人源化小鼠以及灵长类动物模型。但是,由于CAR-T细胞产品的个性化程度高,人和动物免疫系统特性存在差异,人源细胞在动物体内易受到免疫排斥等原因,人源产品在动物模型上的研究结果尚不能完全反映其在人体内的作用情况。因此,需要根据产品特点和研究目的,构建或者选择适当的动物模型,为CAR-T细胞治疗产品非临床研究提供有效的研究工具。
英文摘要:
      Chimeric antigen receptor T cells (CAR-T) has become a research focus in the field of cancer immunotherapy in recent years. Because of its high specificity and strong selectivity, CAR-T has great potential in the field of cancer therapy. However, CAR-T therapy can have specific toxic risks, including cytokine release syndrome, neurotoxicity, B-cell reduction, as well as targeted and off-target toxicity. It is crucial to obtain nonclinical information such as the effectiveness and safety of CAR-T products in the early stages of R&D prior to human use. Selecting appropriate animal models for these above-mentioned studies can greatly improve the predictability of clinical outcomes. At present, the animal models that have been used for CAR-T product research and still are in the exploratory stage mainly include including homologous mouse models, transgenic mice,mouse models of transplanted tumors, humanized mouse with reconstructed immune system, and primate models. However, due to the high degree of personalization of CAR-T cell products, human-derived cells are susceptible to immune rejection in animals, and differences of biological characteristics and immune system between humans and animals, etc., human-derived product studied in animal models could not fully reflect its role in the human body. Therefore, it is necessary to construct or select appropriate animal models based on product characteristics and research purposes, and to provide powerful tools for non-clinical study of CAR-T cell therapy products.
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