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精准靶向肿瘤:TCR 工程化 T 细胞治疗的策略洞见

英文原题:Targeting cancer with precision: strategical insights into TCR-engineered T cell therapies.

查看英文原题

Targeting cancer with precision: strategical insights into TCR-engineered T cell therapies.

PubMed 2025/01/01(内容时间) Theranostics Q1 · IF 14.9(JCR 2025)

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中文摘要

T细胞受体工程化T(TCR-T)细胞疗法处于癌症免疫治疗前沿,可显著增强T细胞识别和清除癌细胞的能力,是一种具有变革性潜力的方法。该策略通过基因改造提高TCR对肿瘤特异性抗原的亲和力。尽管这种增强可提高T细胞识别并结合癌细胞抗原的能力,仍须严格评估特异性,以确保安全并实现靶向应答。兼顾亲和力和特异性,有望精准、高效地识别癌细胞,尤其适用于实体瘤。尽管TCR工程快速发展、TCR筛选技术显著进步,且进入临床试验的特异性TCR数量不断增加,该领域仍存在若干技术和临床挑战,主要涉及工程化TCR的特异性、亲和力和安全性。准确识别并筛选兼具疗效和安全性的TCR,对TCR-T细胞疗法成功治疗癌症至关重要。本文全面回顾TCR疗法的理论基础,探讨筛选特异性TCR及抗原的策略,并重点介绍这一不断发展的治疗领域面临的挑战。

展开英文摘要原文

T cell receptor-engineered T (TCR-T) cell therapies are at the forefront of cancer immunotherapy, offering a transformative approach that significantly enhances the ability of T cells to recognize and eliminate cancer cells. This innovative method involves genetically modifying TCRs to increase their affinity for tumor-specific antigens. While these enhancements improve the ability of T cells to recognize and bind to antigens on cancer cells, rigorous assessment of specificity remains crucial to ensure safety and targeted responses.

This dual focus on affinity and specificity holds significant promise for the treatment of solid tumors, enabling precise and efficient cancer cell recognition. Despite rapid advancements in TCR engineering and notable progress in TCR screening technologies, as evidenced by the growing number of specific TCRs entering clinical trials, several technical and clinical challenges remain. These challenges primarily pertain to the specificity, affinity, and safety of engineered TCRs.

Moreover, the accurate identification and selection of TCRs that are both effective and safe are essential for the success of TCR-T cell therapies in cancer treatment. This review provides a comprehensive examination of the theoretical foundations of TCR therapy, explores strategies for screening specific TCRs and antigens, and highlights the ongoing challenges in this evolving therapeutic landscape.

论文信息

作者
Lin P、Lin Y、Mai Z、Zheng Y、Zheng J、Zhou Z、Zhao X、Cui L
单位
Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China.China
文献类型
综述 · 非美国政府资助研究
期刊
Theranostics2025
原文标识
PubMed 39744228 · DOI 10.7150/thno.104594