He Wanjun, Cui Kai, Farooq Muhammad Asad, Huang Na, Zhu Songshan, Jiang Dan, Zhang Xiqian, Chen Jian, Liu Yinxia, Xu Guangxian
Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, China.
Dongguan Key Laboratory of Molecular Immunology and Cell Therapy, Guangdong Medical University, Dongguan, China.
Front Pharmacol. 2025 Mar 10;16:1493346. doi: 10.3389/fphar.2025.1493346. eCollection 2025.
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.
近年来,随着T细胞受体T细胞(TCR-T细胞)和嵌合抗原受体T细胞(CAR-T细胞)的应用,癌症的T细胞免疫疗法取得了显著进展。CAR-T细胞疗法在治疗血液系统恶性肿瘤时已显示出非凡的成效。然而,仍有一些障碍阻碍了这一成果应用于实体瘤,比如肿瘤靶向方面的挑战以及基因改造T细胞的转运和适应不足,尤其是在不利的肿瘤微环境中。TCR-T细胞弥补了CAR-T细胞疗法在治疗实体瘤方面的不足,TCR-T细胞具有更强的归巢能力以启动细胞内指令,90%的蛋白质可用作开发靶点,并且它们能更广泛地识别靶抗原。因此,TCR-T细胞在治疗实体瘤方面可能更有效。在本综述中,我们讨论了TCR-T的结构,概述了TCR-T在癌症治疗中的缺点,并提出了潜在的补救措施。本综述对于理解TCR-T细胞疗法的现状和未来潜力至关重要。我们强调采用组合方法的重要性,即将各种新兴策略的新组合与为TCR-T设计的非处方疗法相结合,以提高TCR-T在肿瘤微环境中的抗肿瘤疗效并最大限度地提高治疗安全性,特别是在实体瘤免疫疗法方面。
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