个性化新抗原癌症疫苗:当前的进展、挑战和光明的未来。

IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Da-Wei Wu, Shuo-Peng Jia, Shu-Jun Xing, Hai-Lan Ma, Xin Wang, Qi-Yu Tang, Zi-Wei Li, Qing Wu, Min Bai, Xin-Yong Zhang, Xiao-Feng Fu, Ming-Ming Jia, Yu Tang, Li Chen, Ning Li
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引用次数: 0

摘要

肿瘤新抗原具有特异性免疫原性,基于新抗原的个性化治疗疫苗在一些临床试验中显示出良好的效果,具有广阔的应用前景。然而,该领域发展迅速,目前相关综述文章较少。总结和分析全球个性化新抗原疫苗临床试验的现状将为药物开发的所有利益相关者提供重要数据。基于Trialtrove数据库,我们以2022年底前启动的新辅助治疗和辅助治疗抗PD-1/PD-L1临床试验数量为关键指标进行了回顾性分析。研究还调查了新发起试验的时间趋势。总结了这些试验的发起者类型、所在国、治疗模式、联合策略、试验药物和靶向癌症类型。截至 2022 年 12 月,共有 199 项试验被纳入分析范围。在这些研究中,I期研究最多(119项,占59.8%),自2015年以来,I期研究一直是最主要的研究类型。多肽疫苗是最大的新抗原疫苗类型,占所有临床试验的 64.8%。根据多肽递送平台,DC 系统的试验比例最高(32 项,16.1%),其次是 LNP(11 项,5.5%)、LPX(11 项,5.5%)和病毒(7 项,3.5%)。大多数疫苗在试验中作为单一疗法使用(133/199,66.8%),而联合免疫治疗药物是最常见的联合疗法形式。就适应症而言,涉及三种或三种以上未指定实体瘤的试验最多(50/199,25.1%),其次是非小细胞肺癌(24/199,12.1%)和胰腺癌(15/199,7.5%)。个性化新抗原癌症疫苗的临床开发仍处于早期阶段。给药系统明显从多肽转向直流电和脂质体平台,其中亚洲的研究数量最多,共同标志着该领域进入了一个新时代。辅助或维持治疗以及与 ICIs 的联合治疗正成为重要的临床开发方向。随着肿瘤免疫相互作用研究的深入,新抗原疫苗的设计、开发和应用必将迅速发展,为未来的肿瘤治疗带来一场新的革命。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Personalized neoantigen cancer vaccines: current progression, challenges and a bright future.

Tumor neoantigens possess specific immunogenicity and personalized therapeutic vaccines based on neoantigens which have shown promising results in some clinical trials, with broad application prospects. However, the field is developing rapidly and there are currently few relevant review articles. Summarizing and analyzing the status of global personalized neoantigen vaccine clinical trials will provide important data for all stakeholders in drug development. Based on the Trialtrove database, a retrospective analysis was conducted using trial quantity as a key indicator for neo-adjuvant and adjuvant therapy anti-PD-1/PD-L1 clinical trials initiated before the end of 2022. The time trend of newly initiated trials was investigated. The sponsor type, host country, treatment mode, combination strategy, tested drugs, and targeted cancer types of these trials were summarized. As of December 2022, a total of 199 trials were included in the analysis. Among these studies, Phase I studies were the most numerous (119, 59.8%), and Phase I studies have been the predominant study type since 2015. Peptide vaccines were the largest neoantigen vaccines type, accounting for 64.8% of all clinical trials. Based on peptide delivery platforms, the proportion of trials was highest for the DC system (32, 16.1%), followed by LNP (11, 5.5%), LPX (11, 5.5%), and viruses (7, 3.5%). Most vaccines were applied in trials as a monotherapy (133/199, 66.8%), meanwhile combining immunotherapeutic drugs was the most common form for combination therapy. In terms of indications, the largest number of trials involved three or more unspecified solid tumors (50/199, 25.1%), followed by non-small cell lung cancer (24/199, 12.1%) and pancreatic cancer (15/199, 7.5%). The clinical development of personalized neoantigen cancer vaccines is still in the early stage. A clear shift in delivery systems from peptides to DC and liposomal platforms, with the largest number of studies in Asia, collectively marks a new era in the field. The adjuvant or maintenance therapy, and the combination treatment with ICIs are becoming the important clinical development orientation. As research on tumor-immune interactions intensifies, the design, development, and application of neoantigen vaccines are bound to develop rapidly, which will bring a new revolution in the future cancer treatment.

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来源期刊
Clinical and Experimental Medicine
Clinical and Experimental Medicine 医学-医学:研究与实验
CiteScore
4.80
自引率
2.20%
发文量
159
审稿时长
2.5 months
期刊介绍: Clinical and Experimental Medicine (CEM) is a multidisciplinary journal that aims to be a forum of scientific excellence and information exchange in relation to the basic and clinical features of the following fields: hematology, onco-hematology, oncology, virology, immunology, and rheumatology. The journal publishes reviews and editorials, experimental and preclinical studies, translational research, prospectively designed clinical trials, and epidemiological studies. Papers containing new clinical or experimental data that are likely to contribute to changes in clinical practice or the way in which a disease is thought about will be given priority due to their immediate importance. Case reports will be accepted on an exceptional basis only, and their submission is discouraged. The major criteria for publication are clarity, scientific soundness, and advances in knowledge. In compliance with the overwhelmingly prevailing request by the international scientific community, and with respect for eco-compatibility issues, CEM is now published exclusively online.
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