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TCR 工程化 T 细胞的肿瘤治疗:当前策略、挑战与前景

英文原题:Cancer Therapy With TCR-Engineered T Cells: Current Strategies, Challenges, and Prospects.

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Cancer Therapy With TCR-Engineered T Cells: Current Strategies, Challenges, and Prospects.

PubMed 2022/03/03(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

为使T细胞重新靶向肿瘤细胞,可在体外工程化改造T细胞,使其表达癌抗原特异性T细胞受体(TCR),生成TCR工程化T细胞(TCR T)。与嵌合抗原受体(CAR)不同,TCR可识别由人类白细胞抗原(HLA)呈递、来源于细胞各区室蛋白的肽段。随着过继细胞疗法(ACT)治疗实体瘤的研究不断加强,TCR T细胞ACT受到越来越多关注。本文介绍CAR和TCR介导的T细胞抗原识别及信号转导机制差异,概述当前TCR T疗法识别的癌症抗原类别,并讨论抗原特异性TCR的发现、增强和验证方面的经典及新兴临床前策略。最后,本文综述TCR T疗法的当前临床试验格局,并讨论现有结果对未来工程化TCR策略开发的启示。

展开英文摘要原文

To redirect T cells against tumor cells, T cells can be engineered ex vivo to express cancer-antigen specific T cell receptors (TCRs), generating products known as TCR-engineered T cells (TCR T). Unlike chimeric antigen receptors (CARs), TCRs recognize HLA-presented peptides derived from proteins of all cellular compartments.

The use of TCR T cells for adoptive cellular therapies (ACT) has gained increased attention, especially as efforts to treat solid cancers with ACTs have intensified. In this review, we describe the differing mechanisms of T cell antigen recognition and signal transduction mediated through CARs and TCRs.

We describe the classes of cancer antigens recognized by current TCR T therapies and discuss both classical and emerging pre-clinical strategies for antigen-specific TCR discovery, enhancement, and validation.

Finally, we review the current landscape of clinical trials for TCR T therapy and discuss what these current results indicate for the development of future engineered TCR approaches.

论文信息

作者
Shafer P、Kelly LM、Hoyos V
单位
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, United States.United States
文献类型
非美国政府资助研究 · 美国政府(非公共卫生署)资助研究 · 综述
期刊
Frontiers in immunology2022
原文标识
PubMed 35309357 · DOI 10.3389/fimmu.2022.835762