肿瘤新抗原疫苗的设计与优化策略

涂辉阳; 韩为东; 张斌

doi:10.12211/2096-8280.2023-060

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肿瘤新抗原疫苗的设计与优化策略

特约评述 | 更新时间：2025-03-20

- 肿瘤新抗原疫苗的设计与优化策略
  封面论文
- Strategies for the design and optimization of tumor neoantigen vaccines
- 合成生物学 2024年5卷第2期页码：254-266
- 作者机构：
  
  1.中国人民解放军总医院第一医学中心生物治疗科，北京 100039
  2.九江市第一人民医院肿瘤科，江西九江 332000
  3.中国人民解放军总医院第五医学中心血液病医学部，造血干细胞治疗及转化研究北京市重点实验室，北京 100071
- 作者简介：
  
  [ "涂辉阳（1988—），男，博士研究生。研究方向为肿瘤免疫治疗。E-mail：417438258@qq.com" ]
  [ "张斌（1970—），男，研究员，博士生导师。研究方向为血干细胞移植、干细胞研究与转化应用、肿瘤免疫细胞治疗等。E-mail：zb307ctc@163.com" ]
- 基金信息：
- DOI：10.12211/2096-8280.2023-060
  中图分类号： R730.51
- 收稿：2023-08-25，
  
  修回：2023-11-12，
  
  纸质出版：2024-04-30
- 稿件说明：
移动端阅览
涂辉阳，韩为东，张斌. 肿瘤新抗原疫苗的设计与优化策略［J］. 合成生物学， 2024， 5（2）： 254-266

TU Huiyang， HAN Weidong， ZHANG Bin. Strategies for the design and optimization of tumor neoantigen vaccines［J］. Synthetic Biology Journal， 2024， 5（2）： 254-266
涂辉阳，韩为东，张斌. 肿瘤新抗原疫苗的设计与优化策略［J］. 合成生物学， 2024， 5（2）： 254-266 DOI： 10.12211/2096-8280.2023-060.

TU Huiyang， HAN Weidong， ZHANG Bin. Strategies for the design and optimization of tumor neoantigen vaccines［J］. Synthetic Biology Journal， 2024， 5（2）： 254-266 DOI： 10.12211/2096-8280.2023-060.

摘要

随着免疫检查点抑制剂和嵌合抗原受体T细胞疗法在不同适应证中的研究和临床应用，免疫治疗已经彻底改变了多种肿瘤的治疗方式。肿瘤新抗原疫苗作为一种前景广阔的免疫治疗方法，旨在激发针对新抗原的特异性T细胞反应。新抗原具有高度特异性，能够诱导和扩展肿瘤特异性T细胞库，即表位扩展。初步临床研究表明，通过快速、经济、高效的合成生物学技术，新抗原肿瘤疫苗已经展现出强大的肿瘤特异性免疫原性和抗肿瘤活性的初步证据。本文详细探讨了肿瘤新抗原的来源、发现与鉴定，以及新抗原疫苗的分类和免疫接种方案。还总结了肿瘤新抗原疫苗的优化策略，包括对预测算法、疫苗结构、免疫原性、给药方式和递送系统等方面的优化，以及联合佐剂、放化疗、免疫检查点抑制剂等方式，为个性化免疫疗法的发展提供了新的思路。

Abstract

With the research progress and clinical application of immune checkpoint inhibitors and chimeric antigen receptor T-cell therapies

immunotherapy has substantially changed the treating modalities for various tumors. Tumor neoantigen vaccines

as a promising immunotherapy method

aim to trigger a novel T cell response against neoantigens. Neoantigens

with their high specificity

can induce and expand the tumor-specific T cell receptor repertoire

which were discovered through the second-generation sequencing of DNA extracted from both the patient’s tumor and non-tumor tissue samples. The sequences and HLA types are then analyzed for alignment to pinpoint tumor-specific mutations. To validate the significance of these mutations

RNA sequencing data are integrated with the results. Subsequently

bioinformatics platforms are employed for the prediction and analysis of neoantigens encoded by mutated genes and HLA types

enabling the identification of potentia

l immunogenic neoantigens. Finally

the immunogenicity of these neoantigens is assessed through techniques such as ELISPOT and tetramer assays. Tumor vaccines can be categorized as peptide-based

DNA-based

RNA-based

and DC-based products. Viruses

lipid nanoparticles

and nano delivery systems can activate antigen-presenting cells

enhancing their ability to recognize and present tumor-associated antigens

thus promoting the activation of CD8

T cells. Neoantigen vaccines can be administered through various routes

including subcutaneous injection

intramuscular injection

intraperitoneal injection

intradermal injection

intravenous injection

or intralymphatic injection. Preliminary clinical studies have shown that neoantigen tumor vaccines have demonstrated evidence of strong tumor-specific immunogenicity and antitumor activity. In this review

we summarize in detail the source

prediction

and identification of tumor neoantigens

as well as the classification and immunization scheme of neoantigen vaccines. In addition

we highlight strategies for optimizing tumor neoantigen vaccines

including prediction algorithms

expressing multiple epitope structures

increasing immunogenicity

administration methods and delivery systems

and combining adjuvants and various treatments

providing new insights for the development of personalized immunotherapy.

关键词

Keywords

references

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