Adeno-Associated Viral Vectors for Homology-Directed Generation of CAR-T Cells.,Biotechnology Journal

当前位置： X-MOL 学术 › Biotechnol. J. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Adeno-Associated Viral Vectors for Homology-Directed Generation of CAR-T Cells.
Biotechnology Journal ( IF 3.2 ) Pub Date : 2019-11-19 , DOI: 10.1002/biot.201900286
Pablo D Moço ₁ , Noga Aharony ₁ , Amine Kamen ₁

Affiliation

Immunotherapy with T cells expressing chimeric antigen receptors (CAR) is an emerging and promising treatment against refractory cancers. However, the currently adopted methods of modification of T cells pose a risk of insertional oncogenesis because lentiviral and retroviral vectors integrate the CAR transgene in a semi-random fashion. In addition, this therapy is only available using autologous cells, which create problems in production and limit the access for patients who have their T cells depleted. One modification method that shows the ability to overcome both drawbacks is the knock-in of the CAR simultaneously knocking-out genes that prevent allogeneic therapy, such as the endogenous T cell receptor. In this mini-review, the authors present recent efforts to develop safer universal CAR-T cells. More specifically, the combined application of target-directed nucleases, which create a double-strand break at a specific genome locus, and the delivery of CAR DNA via adeno-associated viral vectors for subsequent integration via homologous recombination and silencing of the targeted gene is focused on.

中文翻译：

腺相关病毒载体，用于同源性指导的CAR-T细胞的产生。

表达嵌合抗原受体（CAR）的T细胞的免疫疗法是一种针对难治性癌症的新兴治疗方法。然而，由于慢病毒和逆转录病毒载体以半随机方式整合了CAR转基因，因此当前采用的修饰T细胞的方法存在插入肿瘤发生的风险。此外，该疗法仅可用于自体细胞，这会在生产中产生问题，并限制T细胞被耗尽的患者进入。一种具有克服上述两个缺点的能力的修饰方法是敲入CAR，同时敲除阻止异基因治疗的基因，例如内源性T细胞受体。在这份小型综述中，作者们提出了开发更安全的通用CAR-T细胞的最新努力。进一步来说，

更新日期：2019-11-20

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11