Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Curr Opin Immunol. 2022 Feb;74:76-84. doi: 10.1016/j.coi.2021.10.008. Epub 2021 Nov 16.
T cells engineered to express transgenes such as chimeric antigen receptors (CAR) or modified T cell receptors (TCR) represent a new pillar of cancer therapy. Use of CRISPR/Cas gene-editing tools now allows even stronger and more precise control over the fate and function of engineered T cell therapies, including multiplex genome editing to facilitate use of off-the-shelf allogeneic T cells and novel approaches which have the potential to overcome some of the limitations of canonical Cas9-mediated DNA cleavage. This review summarizes the CRISPR/Cas techniques that have been used in preclinical research and outlines those that currently being tested in clinical trials.
经基因工程改造表达嵌合抗原受体(CAR)或修饰的 T 细胞受体(TCR)等转基因的 T 细胞代表癌症治疗的一个新支柱。CRISPR/Cas 基因编辑工具的使用甚至可以对工程化 T 细胞疗法的命运和功能进行更强有力和更精确的控制,包括多重基因组编辑以促进使用现成的同种异体 T 细胞和具有潜在克服一些经典 Cas9 介导的 DNA 切割的局限性的新方法。本文综述了已在临床前研究中使用的 CRISPR/Cas 技术,并概述了目前正在临床试验中测试的技术。