Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Mol Ther. 2018 Jan 3;26(1):280-288. doi: 10.1016/j.ymthe.2017.09.008. Epub 2017 Sep 12.
Exposure to replication-competent lentivirus (RCL) is a theoretical safety concern for individuals treated with lentiviral gene therapy. For certain ex vivo gene therapy applications, including cancer immunotherapy trials, RCL detection assays are used to screen the vector product as well as the vector-transduced cells. In this study, we reviewed T cell products screened for RCL using methodology developed in the National Gene Vector Biorepository. All trials utilized third-generation lentiviral vectors produced by transient transfection. Samples from 26 clinical trials totaling 460 transduced cell products from 375 subjects were evaluated. All cell products were negative for RCL. A total of 296 of the clinical trial participants were screened for RCL at least 1 month after infusion of the cell product. No research subject has shown evidence of RCL infection. These findings provide further evidence attesting to the safety of third-generation lentiviral vectors and that testing T cell products for RCL does not provide added value to screening the lentiviral vector product.
暴露于复制型慢病毒（RCL）是接受慢病毒基因治疗的个体的一个理论安全性问题。对于某些离体基因治疗应用，包括癌症免疫治疗试验，使用 RCL 检测分析来筛选载体产品以及载体转导细胞。在这项研究中，我们回顾了使用国家基因载体生物库开发的方法筛选 RCL 的 T 细胞产品。所有试验均使用瞬时转染产生的第三代慢病毒载体。评估了来自 375 名受试者的 26 项临床试验共 460 个转导细胞产品的样本。所有细胞产品均未检测到 RCL。共有 296 名临床试验参与者在输注细胞产品后至少 1 个月接受了 RCL 筛查。没有研究对象显示出 RCL 感染的证据。这些发现进一步证明了第三代慢病毒载体的安全性，并且对 RCL 进行 T 细胞产品筛选不会为筛选慢病毒载体产品提供额外价值。
