文章摘要
吴雪伶,赵翔,孟淑芳.CAR-T细胞治疗产品中复制型病毒的风险分析及控制[J].中国药事,2018,32(7):879-885
CAR-T细胞治疗产品中复制型病毒的风险分析及控制
Risk Analysis and Control of Replication Competent Virus in CAR-T Cell Therapy Products
投稿时间:2018-06-21  
DOI:10.16153/j.1002-7777.2018.07.006
中文关键词: 嵌合抗原修饰T细胞(CAR-T细胞)  逆转录病毒载体  慢病毒载体  复制型病毒
英文关键词: chimeric antigen receptor T cell (CAR-T)  retroviral vectors  lentiviral vectors  replication competent virus
基金项目:国家科技重大专项“创新生物技术药评价及标准化关键技术研究”(编号2018ZX09101001)
作者单位E-mail
吴雪伶 中国食品药品检定研究院, 国家卫生健康委员会生物技术产品检定方法及其标准化重点实验室, 北京 100050  
赵翔 中国食品药品检定研究院, 国家卫生健康委员会生物技术产品检定方法及其标准化重点实验室, 北京 100050  
孟淑芳 中国食品药品检定研究院, 国家卫生健康委员会生物技术产品检定方法及其标准化重点实验室, 北京 100050 mengsf@263.net 
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中文摘要:
      嵌合抗原受体T细胞(CAR-T细胞)因其在血液肿瘤中的显著疗效已成为肿瘤免疫治疗领域中的国际研究新热点,成为肿瘤治愈新的希望。目前,在CAR-T细胞产品的生产中,通常是利用逆转录病毒载体或慢病毒载体将CAR基因高效地导入T细胞中,但在使用这些病毒载体的同时也带来了CAR-T产品污染复制型逆转录病毒(RCR)或复制型慢病毒(RCL)的潜在风险。虽然随着病毒载体设计及生产体系的不断改进,这种风险已大大降低,但仍不能完全排除。因此,监管机构要求对于临床使用的慢病毒或逆转录病毒载体、转导的CAR-T细胞产品以及患者均要进行复制型病毒的检测。本文主要通过分析复制型病毒污染检测的必要性、降低复制型病毒污染风险的措施、复制型病毒检测的阶段以及检测方法等方面,提出在CAR-T细胞生产过程中控制RCR/RCL的策略,以供CAR-T细胞产品研发者参考。
英文摘要:
      Chimeric antigen receptor T cell (CAR-T) has become a new research focus in the field of tumor immunotherapy due to its remarkable therapeutic effects in hematological tumors, and has become a new hope for the cure of cancer. At present, retroviral vectors or lentiviral vectors are commonly used to efficiently introduce CAR gene into T cells in the production of CAR-T cell products. However, the use of these vectors may cause the risk of contamination of CAR-T cell products with replication competent retroviruses (RCR) or replication competent lentiviruses (RCL). Although this risk has been greatly reduced with the continuous improvement of virus vector design and production systems, it cannot be completely eliminated. Therefore, Regulatory agencies require the detection of replicative viruses for the clinically used lentivirus or retroviral vectors, transduced CAR-T cell products and patients. This article mainly focuses on the necessity of the replication competent virus contamination detection, the measures to reduce the risk of replication competent virus pollution, the stage of replication competent virus detection and the detection methods, and putting forward the consideration for controlling RCR/RCL in the process of CAR-T cell production for reference by CAR-T cell product developers.
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