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实体瘤的 TCR-T 细胞疗法:挑战与新兴解决方案

英文原题:TCR-T cell therapy for solid tumors: challenges and emerging solutions.

查看英文原题

TCR-T cell therapy for solid tumors: challenges and emerging solutions.

PubMed 2025/03/10(内容时间) Front Pharmacol Q1 · IF 5.4(JCR 2025)

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中文摘要

近年来,利用 T 细胞受体 T 细胞(TCR-T)和CAR-T 细胞,癌症 T 细胞免疫治疗已取得显著进展。CAR-T 治疗血液系统恶性肿瘤获得了非凡成功,但仍有多个障碍阻碍这一成果向实体瘤拓展,例如肿瘤靶向挑战,以及基因修饰 T 细胞迁移和适应能力不足,尤其是在不利的肿瘤微环境中。TCR-T 可弥补 CAR-T 治疗实体瘤的部分不足:其归巢能力更强,可启动细胞内信号,并且约 90% 的蛋白质都可作为开发靶点,能够识别范围更广的靶抗原。

因此,TCR-T 可能更适用于实体瘤治疗。本综述介绍 TCR-T 的结构,概述其用于癌症治疗的不足并提出潜在解决方案,有助于理解 TCR-T 细胞疗法现状及未来潜力。

我们强调采用组合策略的重要性,即将不同新兴策略与专为 TCR-T 设计的现有疗法结合,以增强 TCR-T 在肿瘤微环境(TME)中的抗肿瘤效力,并最大限度提高治疗安全性,尤其是在实体瘤免疫治疗中。

展开英文摘要原文

With the use of T cell receptor T cells (TCR-T cells) and chimeric antigen receptor T cells (CAR-T cells), T-cell immunotherapy for cancer has advanced significantly in recent years. CAR-T cell therapy has demonstrated extraordinary success when used to treat hematologic malignancies. Nevertheless, there are several barriers that prevent this achievement from being applied to solid tumors, such as challenges with tumor targeting and inadequate transit and adaption of genetically modified T-cells, especially in unfavorable tumor microenvironments The deficiencies of CAR-T cell therapy in the treatment of solid tumors are compensated for by TCR-T cells, which have a stronger homing ability to initiate intracellular commands, 90% of the proteins can be used as developmental targets, and they can recognize target antigens more broadly.

As a result, TCR-T cells may be more effective in treating solid tumors. In this review, we discussed the structure of TCR-T and have outlined the drawbacks of TCR-T in cancer therapy, and suggested potential remedies. This review is crucial in understanding the current state and future potential of TCR-T cell therapy.

We emphasize how important it is to use combinatorial approaches, combining new combinations of various emerging strategies with over-the-counter therapies designed for TCR-T, to increase the anti-tumor efficacy of TCR-T inside the TME and maximize treatment safety, especially when it comes to solid tumor immunotherapies.

论文信息

作者
He W、Cui K、Farooq MA、Huang N、Zhu S、Jiang D、Zhang X、Chen J
单位
Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, China.China
文献类型
综述
期刊
Frontiers in pharmacology2025
原文标识
PubMed 40129944 · DOI 10.3389/fphar.2025.1493346