Neoantigen identification and TCR-T therapy development for solid tumors: current advances and future perspectives

IF 9.4 Q1 ONCOLOGY
Xinyao Zheng, Yahui Zhao, Zhihua Liu
{"title":"Neoantigen identification and TCR-T therapy development for solid tumors: current advances and future perspectives","authors":"Xinyao Zheng,&nbsp;Yahui Zhao,&nbsp;Zhihua Liu","doi":"10.1016/j.jncc.2025.07.001","DOIUrl":null,"url":null,"abstract":"<div><div>Recently, T cells expressing engineered T cell receptor (TCR-T cells) have become recognized as a promising tumor cell therapy for solid tumors because of their ability to selectively kill tumor cells with less destruction of other cells and their high safety when used as autologous T cells. Several studies and clinical tests have been conducted to demonstrate its potential as a novel therapy. However, previous research has mainly focused on antigens; these common targets for TCR-T are tumor-associated antigens, which exhibit expression not only in tumor cells but also in normal cells, resulting in off-target risk and not considering the heterogeneity of different patients. In contrast, neoantigens offer superior specificity as they are uniquely expressed on tumor cells due to genomic alterations. Given the frequent occurrence and notable role of genetic mutations in tumorigenesis and tumor progression, identification and targeting of neoantigens is a valuable therapeutic direction. This perspective delves into various antigen classifications, including their characteristics and advantages, as well as strategies for identifying and validating neoantigens that have emerged from numerous research studies. These insights are crucial for guiding the search for new neoantigens. We also review significant and representative studies involving TCR-T and other immunotherapies that target neoantigens to assess the therapeutic effectiveness of TCR-T therapy. Moreover, we discuss the challenges and complexities inherent in TCR-T therapy and propose potential solutions for these issues. In this perspective, we aim to provide fresh perceptions and strategies for cancer treatment by highlighting the potential of TCR-T and exploring its challenges and future directions. It also seeks to propel the development of precision medicine and personalized therapy, offering hope for more effective and targeted cancer treatments in the future.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 5","pages":"Pages 429-440"},"PeriodicalIF":9.4000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the National Cancer Center","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2667005425000833","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Recently, T cells expressing engineered T cell receptor (TCR-T cells) have become recognized as a promising tumor cell therapy for solid tumors because of their ability to selectively kill tumor cells with less destruction of other cells and their high safety when used as autologous T cells. Several studies and clinical tests have been conducted to demonstrate its potential as a novel therapy. However, previous research has mainly focused on antigens; these common targets for TCR-T are tumor-associated antigens, which exhibit expression not only in tumor cells but also in normal cells, resulting in off-target risk and not considering the heterogeneity of different patients. In contrast, neoantigens offer superior specificity as they are uniquely expressed on tumor cells due to genomic alterations. Given the frequent occurrence and notable role of genetic mutations in tumorigenesis and tumor progression, identification and targeting of neoantigens is a valuable therapeutic direction. This perspective delves into various antigen classifications, including their characteristics and advantages, as well as strategies for identifying and validating neoantigens that have emerged from numerous research studies. These insights are crucial for guiding the search for new neoantigens. We also review significant and representative studies involving TCR-T and other immunotherapies that target neoantigens to assess the therapeutic effectiveness of TCR-T therapy. Moreover, we discuss the challenges and complexities inherent in TCR-T therapy and propose potential solutions for these issues. In this perspective, we aim to provide fresh perceptions and strategies for cancer treatment by highlighting the potential of TCR-T and exploring its challenges and future directions. It also seeks to propel the development of precision medicine and personalized therapy, offering hope for more effective and targeted cancer treatments in the future.
实体瘤的新抗原鉴定和TCR-T治疗发展:当前进展和未来展望
近年来,表达工程化T细胞受体的T细胞(TCR-T细胞)因其选择性杀死肿瘤细胞而对其他细胞破坏较小以及作为自体T细胞使用时具有较高的安全性而被认为是一种很有前景的实体瘤肿瘤细胞治疗方法。已经进行了一些研究和临床试验,以证明其作为一种新疗法的潜力。然而,以前的研究主要集中在抗原上;这些TCR-T的共同靶点是肿瘤相关抗原,这些抗原不仅在肿瘤细胞中表达,也在正常细胞中表达,导致脱靶风险,并且没有考虑不同患者的异质性。相比之下,由于基因组改变,新抗原在肿瘤细胞上独特表达,因此具有优越的特异性。鉴于基因突变在肿瘤发生和进展中的频繁发生和重要作用,新抗原的识别和靶向治疗是一个有价值的治疗方向。这一观点深入探讨了各种抗原分类,包括它们的特点和优势,以及识别和验证新抗原的策略,这些新抗原已经从许多研究中出现。这些见解对于指导寻找新的新抗原至关重要。我们还回顾了涉及TCR-T和其他针对新抗原的免疫疗法的重要和有代表性的研究,以评估TCR-T疗法的治疗效果。此外,我们讨论了TCR-T疗法固有的挑战和复杂性,并提出了这些问题的潜在解决方案。从这个角度来看,我们的目标是通过强调TCR-T的潜力,探索其挑战和未来的方向,为癌症治疗提供新的认识和策略。它还寻求推动精准医学和个性化治疗的发展,为未来更有效、更有针对性的癌症治疗提供希望。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
14.20
自引率
0.00%
发文量
0
审稿时长
70 days
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信