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[通用嵌合抗原受体T细胞的研发]

[Development of universal CAR-T cells].

作者信息

Kagoya Yuki, Hirano Naoto

机构信息

Division of Immune Response, Aichi Cancer Center Research Institute.

Division of Cellular Oncology, Department of Cancer Diagnostics and Therapeutics, Nagoya University Graduate School of Medicine.

出版信息

Rinsho Ketsueki. 2022;63(7):782-789. doi: 10.11406/rinketsu.63.782.

Abstract

The efficacy of adoptive immunotherapy using CD19-targeting chimeric antigen receptor (CAR)-engineered T cells against B-cell malignancies has already been established in the clinic. However, high economic costs and heterogeneous quality of CAR-T cells derived from individual patients hinder further expansion of their applicability to various cancer types, including solid tumors. Mass CAR-T cell production from healthy donors is a promising approach to overcome these problems, given that allogeneic immunity elicited against donor CAR-T cells by the recipient's immune system is controlled. CAR-T cells genetically ablated with T-cell receptor and human leukocyte antigen molecules, referred to as universal CAR-T cells, may enable the use of allogeneic T cells for off-the-shelf adoptive cancer immunotherapy. However, several concerns, such as poor persistence of infused CAR-T cells and chromosomal abnormalities due to genome editing, remain to be addressed. Thus, recent clinical trials on universal CAR-T cells are summarized and future perspectives to overcome current challenges are discussed in this review.

摘要

使用靶向CD19的嵌合抗原受体(CAR)工程化T细胞进行过继性免疫治疗对B细胞恶性肿瘤的疗效已在临床上得到证实。然而,来自个体患者的CAR-T细胞的高经济成本和异质性质量阻碍了其在包括实体瘤在内的各种癌症类型中的进一步应用扩展。鉴于受者免疫系统对供体CAR-T细胞引发的同种异体免疫得到控制,从健康供体大量生产CAR-T细胞是克服这些问题的一种有前景的方法。用T细胞受体和人类白细胞抗原分子进行基因消融的CAR-T细胞,即通用CAR-T细胞,可能使异体T细胞用于现成可用的过继性癌症免疫治疗。然而,一些问题,如注入的CAR-T细胞持久性差以及由于基因组编辑导致的染色体异常,仍有待解决。因此,本文综述了近期关于通用CAR-T细胞的临床试验,并讨论了克服当前挑战的未来前景。

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