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

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,...

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Main Authors: Wanjun He, Kai Cui, Muhammad Asad Farooq, Na Huang, Songshan Zhu, Dan Jiang, Xiqian Zhang, Jian Chen, Yinxia Liu, Guangxian Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1493346/full
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author Wanjun He
Wanjun He
Kai Cui
Kai Cui
Muhammad Asad Farooq
Na Huang
Na Huang
Songshan Zhu
Songshan Zhu
Dan Jiang
Dan Jiang
Xiqian Zhang
Xiqian Zhang
Xiqian Zhang
Jian Chen
Yinxia Liu
Guangxian Xu
Guangxian Xu
author_facet Wanjun He
Wanjun He
Kai Cui
Kai Cui
Muhammad Asad Farooq
Na Huang
Na Huang
Songshan Zhu
Songshan Zhu
Dan Jiang
Dan Jiang
Xiqian Zhang
Xiqian Zhang
Xiqian Zhang
Jian Chen
Yinxia Liu
Guangxian Xu
Guangxian Xu
author_sort Wanjun He
collection DOAJ
description 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.
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spelling doaj-art-0be99d2b2f1d4fe8aa2a1e2ab357dcd42025-08-20T02:47:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.14933461493346TCR-T cell therapy for solid tumors: challenges and emerging solutionsWanjun He0Wanjun He1Kai Cui2Kai Cui3Muhammad Asad Farooq4Na Huang5Na Huang6Songshan Zhu7Songshan Zhu8Dan Jiang9Dan Jiang10Xiqian Zhang11Xiqian Zhang12Xiqian Zhang13Jian Chen14Yinxia Liu15Guangxian Xu16Guangxian Xu17Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, ChinaDongguan Key Laboratory of Molecular Immunology and Cell Therapy, Guangdong Medical University, Dongguan, ChinaGuangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, ChinaDongguan Key Laboratory of Molecular Immunology and Cell Therapy, Guangdong Medical University, Dongguan, ChinaGuangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, ChinaGuangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, ChinaDongguan Key Laboratory of Molecular Immunology and Cell Therapy, Guangdong Medical University, Dongguan, ChinaGuangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, ChinaDongguan Key Laboratory of Molecular Immunology and Cell Therapy, Guangdong Medical University, Dongguan, ChinaGuangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, ChinaDongguan Key Laboratory of Molecular Immunology and Cell Therapy, Guangdong Medical University, Dongguan, ChinaGuangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, ChinaDongguan Key Laboratory of Molecular Immunology and Cell Therapy, Guangdong Medical University, Dongguan, ChinaYinchuan Guolong Orthopedic Hospital, Yinchuan, ChinaYinchuan Guolong Orthopedic Hospital, Yinchuan, ChinaGuangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, ChinaGuangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, ChinaDongguan Key Laboratory of Molecular Immunology and Cell Therapy, Guangdong Medical University, Dongguan, ChinaWith 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.https://www.frontiersin.org/articles/10.3389/fphar.2025.1493346/fulladoptive cell therapyimmunotherapysolid tumorTCRTCR-T cell
spellingShingle Wanjun He
Wanjun He
Kai Cui
Kai Cui
Muhammad Asad Farooq
Na Huang
Na Huang
Songshan Zhu
Songshan Zhu
Dan Jiang
Dan Jiang
Xiqian Zhang
Xiqian Zhang
Xiqian Zhang
Jian Chen
Yinxia Liu
Guangxian Xu
Guangxian Xu
TCR-T cell therapy for solid tumors: challenges and emerging solutions
Frontiers in Pharmacology
adoptive cell therapy
immunotherapy
solid tumor
TCR
TCR-T cell
title TCR-T cell therapy for solid tumors: challenges and emerging solutions
title_full TCR-T cell therapy for solid tumors: challenges and emerging solutions
title_fullStr TCR-T cell therapy for solid tumors: challenges and emerging solutions
title_full_unstemmed TCR-T cell therapy for solid tumors: challenges and emerging solutions
title_short TCR-T cell therapy for solid tumors: challenges and emerging solutions
title_sort tcr t cell therapy for solid tumors challenges and emerging solutions
topic adoptive cell therapy
immunotherapy
solid tumor
TCR
TCR-T cell
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1493346/full
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