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为异体 T 细胞的普遍治疗铺平道路。

Paving the way towards universal treatment with allogenic T cells.

机构信息

Department of Microbiology and Molecular Biology, Brigham Young University, 3142 LSB, Provo, UT, 84602, USA.

出版信息

Immunol Res. 2020 Feb;68(1):63-70. doi: 10.1007/s12026-020-09119-7.

DOI:10.1007/s12026-020-09119-7
PMID:32096010
Abstract

With several different CAR T cell therapies under advanced phases of clinical trials, and the first FDA-approved CAR treatments in 2017 (Yescarta and Kymriah), CAR T cell therapy has become one of the most promising therapies for the treatment of certain types of cancer. This success has bred an opportunity to optimize the production of CAR T cells for easier patient access. CAR T cell therapy is a rather expensive and personalized process that requires expensive measures to collect cells from patients, engineer those cells, and re-infuse the cells into the patient with adequate quality controls at each phase. With this in mind, significant attempts at creating a "universal" CAR T cell are underway in order to create an "off-the-shelf" product that would reduce the expense and time required for traditional CAR T cell treatment. The primary obstacle facing this endeavor is avoiding graft-versus-host disease that accompanies allogeneic transplants between genetically dissimilar individuals. With the advent of CRISPR and TALEN technology, editing the genome of allogeneic cells has become very possible, and several groups have provided initial data analyzing the effects of CAR T cells that have been edited to avoid host rejection and avoid endogenous TCR alloreactivity. These engineered cells not only have to avoid GVHD but also have to retain their anti-tumor efficacy in vivo. Here, we expand on the recent efforts and strides that have been made in the design and testing of universal allogeneic CAR T cells.

摘要

随着几种不同的 CAR T 细胞疗法进入临床试验的后期阶段,以及 2017 年首个获得 FDA 批准的 CAR 治疗方法(Yescarta 和 Kymriah),CAR T 细胞疗法已成为治疗某些类型癌症最有前途的疗法之一。这一成功为优化 CAR T 细胞的生产以方便患者获得治疗机会提供了契机。CAR T 细胞疗法是一种相当昂贵和个性化的治疗方法,需要昂贵的措施从患者中收集细胞,对这些细胞进行工程改造,并在每个阶段进行充分的质量控制后将细胞重新注入患者体内。考虑到这一点,正在进行大量的尝试来创建一种“通用”的 CAR T 细胞,以创建一种“现成”的产品,从而降低传统 CAR T 细胞治疗所需的费用和时间。这项工作面临的主要障碍是避免伴随基因不同的个体之间异基因移植的移植物抗宿主病。随着 CRISPR 和 TALEN 技术的出现,编辑异基因细胞的基因组变得非常可行,几个研究小组已经提供了初步数据,分析了经过编辑以避免宿主排斥和避免内源性 TCR 同种异体反应的 CAR T 细胞的效果。这些经过工程改造的细胞不仅要避免移植物抗宿主病,还要在体内保留其抗肿瘤功效。在这里,我们扩展了最近在通用异基因 CAR T 细胞的设计和测试方面所做的努力和取得的进展。

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