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新抗原:癌症治疗的有希望靶点

英文原题:Neoantigens: promising targets for cancer therapy.

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Neoantigens: promising targets for cancer therapy.

PubMed 2023/01/06(内容时间) Signal Transduct Target Ther Q1 · IF 81.2(JCR 2025)

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中文摘要

新抗原研究的近期进展加速了肿瘤免疫疗法的开发和监管批准,包括癌症疫苗、过继性细胞疗法和基于抗体的疗法,尤其是针对实体瘤。新抗原是肿瘤细胞因各种肿瘤特异性改变而产生的新形成的抗原,这些改变包括基因组突变、RNA剪接失调、翻译后修饰紊乱以及整合的病毒开放阅读框。新抗原被识别为非自身,并触发不受中枢和外周耐受限制的免疫应答。下一代测序和生物信息学技术的先进发展使得肿瘤特异性新抗原的快速识别和预测成为可能。与肿瘤相关抗原相比,高免疫原性和肿瘤特异性的新抗原为个体化癌症免疫疗法提供了新兴靶点,并可作为肿瘤生存预后和免疫检查点阻断应答的前瞻性预测指标。理解新抗原诱导抗肿瘤免疫应答的机制并简化基于新抗原的免疫疗法流程,将有助于癌症疗法的开发。本综述概述了新抗原的识别和表征,并概述了基于新抗原的前瞻性免疫治疗策略的临床应用。我们还探讨了其当前状况、固有挑战和临床转化潜力。

展开英文摘要原文

Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy and antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations, such as genomic mutation, dysregulated RNA splicing, disordered post-translational modification, and integrated viral open reading frames. Neoantigens are recognized as non-self and trigger an immune response that is not subject to central and peripheral tolerance. The quick identification and prediction of tumor-specific neoantigens have been made possible by the advanced development of next-generation sequencing and bioinformatic technologies.

Compared to tumor-associated antigens, the highly immunogenic and tumor-specific neoantigens provide emerging targets for personalized cancer immunotherapies, and serve as prospective predictors for tumor survival prognosis and immune checkpoint blockade responses.

The development of cancer therapies will be aided by understanding the mechanism underlying neoantigen-induced anti-tumor immune response and by streamlining the process of neoantigen-based immunotherapies. This review provides an overview on the identification and characterization of neoantigens and outlines the clinical applications of prospective immunotherapeutic strategies based on neoantigens.

We also explore their current status, inherent challenges, and clinical translation potential.

论文信息

作者
Xie N、Shen G、Gao W、Huang Z、Huang C、Fu L
第一作者单位
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.China
通讯作者单位
Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pharmacology and International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 518060, Guangdong, People's Republic of China. gracelfu@szu.edu.cn.China
文献类型
综述 · 非美国政府资助研究
期刊
Signal transduction and targeted therapy2023 Jan 6
原文标识
PubMed 36604431 · DOI 10.1038/s41392-022-01270-x