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实体瘤中TCR-T细胞疗法的新见解:优化过继性免疫疗法。

Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy.

作者信息

Shao Weihuan, Yao Yiran, Yang Ludi, Li Xiaoran, Ge Tongxin, Zheng Yue, Zhu Qiuyi, Ge Shengfang, Gu Xiang, Jia Renbing, Song Xin, Zhuang Ai

机构信息

Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai Ninth People's Hospital, Shanghai, 200011, People's Republic of China.

Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200011, People's Republic of China.

出版信息

Exp Hematol Oncol. 2024 Apr 3;13(1):37. doi: 10.1186/s40164-024-00504-8.

DOI:10.1186/s40164-024-00504-8
PMID:38570883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10988985/
Abstract

Adoptive immunotherapy in the T cell landscape exhibits efficacy in cancer treatment. Over the past few decades, genetically modified T cells, particularly chimeric antigen receptor T cells, have enabled remarkable strides in the treatment of hematological malignancies. Besides, extensive exploration of multiple antigens for the treatment of solid tumors has led to clinical interest in the potential of T cells expressing the engineered T cell receptor (TCR). TCR-T cells possess the capacity to recognize intracellular antigen families and maintain the intrinsic properties of TCRs in terms of affinity to target epitopes and signal transduction. Recent research has provided critical insight into their capability and therapeutic targets for multiple refractory solid tumors, but also exposes some challenges for durable efficacy. In this review, we describe the screening and identification of available tumor antigens, and the acquisition and optimization of TCRs for TCR-T cell therapy. Furthermore, we summarize the complete flow from  laboratory to clinical applications of TCR-T cells. Last, we emerge future prospects for improving therapeutic efficacy in cancer world with combination therapies or TCR-T derived products. In conclusion, this review depicts our current understanding of TCR-T cell therapy in solid neoplasms, and provides new perspectives for expanding its clinical applications and improving therapeutic efficacy.

摘要

在T细胞格局中的过继性免疫疗法在癌症治疗中显示出疗效。在过去几十年里,基因改造的T细胞,特别是嵌合抗原受体T细胞,在血液系统恶性肿瘤的治疗方面取得了显著进展。此外,针对实体瘤治疗对多种抗原的广泛探索引发了临床上对表达工程化T细胞受体(TCR)的T细胞潜力的兴趣。TCR-T细胞具有识别细胞内抗原家族的能力,并在与靶表位的亲和力和信号转导方面保持TCR的固有特性。最近的研究不仅为其针对多种难治性实体瘤的能力和治疗靶点提供了关键见解,也揭示了实现持久疗效面临的一些挑战。在这篇综述中,我们描述了可用肿瘤抗原的筛选和鉴定,以及用于TCR-T细胞疗法的TCR的获取和优化。此外,我们总结了TCR-T细胞从实验室到临床应用的完整流程。最后,我们展望了通过联合疗法或TCR-T衍生产品提高癌症治疗疗效的未来前景。总之,这篇综述阐述了我们目前对实体瘤中TCR-T细胞疗法的理解,并为扩大其临床应用和提高治疗疗效提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/348d/10988985/ca188246a118/40164_2024_504_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/348d/10988985/626f630acbf8/40164_2024_504_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/348d/10988985/109cc58138c0/40164_2024_504_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/348d/10988985/86506a96b1e8/40164_2024_504_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/348d/10988985/ca188246a118/40164_2024_504_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/348d/10988985/626f630acbf8/40164_2024_504_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/348d/10988985/109cc58138c0/40164_2024_504_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/348d/10988985/86506a96b1e8/40164_2024_504_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/348d/10988985/ca188246a118/40164_2024_504_Fig4_HTML.jpg

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Lymph Node-Targeted Vaccine Boosting of TCR T-cell Therapy Enhances Antitumor Function and Eradicates Solid Tumors.淋巴靶向疫苗增强 TCR T 细胞疗法的抗肿瘤功能并根除实体瘤。
Cancer Immunol Res. 2024 Feb 2;12(2):214-231. doi: 10.1158/2326-6066.CIR-22-0978.
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CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial.CLDN6 特异性 CAR-T 细胞联合扩增 RNA 疫苗治疗复发或难治性实体瘤的 I 期 BNT211-01 试验。
Nat Med. 2023 Nov;29(11):2844-2853. doi: 10.1038/s41591-023-02612-0. Epub 2023 Oct 23.
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The BRD4-NUT Fusion Alone Drives Malignant Transformation of NUT Carcinoma.
实体瘤中的免疫调节与免疫治疗:耐药机制及潜在治疗策略
Int J Mol Sci. 2025 Mar 24;26(7):2923. doi: 10.3390/ijms26072923.
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Neoepitope BTLA-specific TCR-T cell immunotherapy unlocks precision treatment for hepatocellular carcinoma.新表位特异性BTLA-TCR-T细胞免疫疗法开启了肝细胞癌的精准治疗。
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ATAD2 is a potential immunotherapy target for patients with small cell lung cancer harboring HLA-A∗0201.对于携带HLA-A∗0201的小细胞肺癌患者,ATAD2是一个潜在的免疫治疗靶点。
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