合成生物学 ›› 2024, Vol. 5 ›› Issue (2): 239-253.DOI: 10.12211/2096-8280.2023-061

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合成生物学在肿瘤疫苗设计中的应用进展

方超1, 黄卫人1,2,3   

  1. 1.中国科学院深圳先进技术研究院,合成生物学研究所,广东 深圳 518035
    2.深圳大学第一附属医院,深圳市第二人民医院,泌尿外科,深圳转化医学研究院,广东 深圳 518035
    3.广东省泌尿生殖肿瘤系统生物学与合成生物学重点实验室,广东 深圳 518035
  • 收稿日期:2023-08-25 修回日期:2024-02-29 出版日期:2024-04-30 发布日期:2024-04-28
  • 通讯作者: 黄卫人
  • 作者简介:方超(1990—),男,博士后。研究方向:(1)肿瘤合成生物学;(2)肿瘤表观遗传学。E-mail:c.fang@siat.ac.cn
    黄卫人(1980—),男,研究员,博士生导师,深圳市转化医学研究院副院长。研究方向:(1)肿瘤基因组学,应用多组学手段鉴定肿瘤及微环境诊疗标志物,开发相关临床应用;(2)肿瘤类器官,利用体外培养系统还原肿瘤体内生长,药物筛选及耐药机制研究;(3)医学合成生物学,创新肿瘤治疗新方法。E-mail:pony8980@163.com
  • 基金资助:
    国家重点研发计划(2019YFA0906003);国家自然科学基金(81972368);广东省培养高层次人才特殊支持计划(2021JC06Y578)

Progress with the application of synthetic biology in designing of cancer vaccines

Chao FANG1, Weiren HUANG1,2,3   

  1. 1.Institute of Synthetic Biology,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518035,Guangdong,China
    2.Department of Urology,The First Affiliated Hospital of Shenzhen University,Shenzhen Second People’s Hospital,Shenzhen Institute of Translational Medicine,Shenzhen 518035,Guangdong,China
    3.Guangdong Provincial Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors,Shenzhen 518035,Guangdong,China
  • Received:2023-08-25 Revised:2024-02-29 Online:2024-04-30 Published:2024-04-28
  • Contact: Weiren HUANG

摘要:

根据中心法则和细胞免疫学原则,利用合成生物学设计和生产新型肿瘤疫苗代表了癌症免疫治疗中的一个重要途径。本文概述了利用合成生物学针对两个主要方面(抗原选择和疫苗设计)的创新治疗性肿瘤疫苗的最新研究进展。针对肿瘤相关或特定抗原,开发更精确和有效的肿瘤疫苗引起了广泛关注。传统方法在抗原选择中主要针对肿瘤中的特定基因,而以高通量测序及质谱为基础筛选新抗原的方法明显改善了疫苗的靶向性及免疫原性。在疫苗类别方面,与传统多肽疫苗相比,通过对DNA、mRNA、病毒/细菌、细胞的工程化修饰而成的新型疫苗显著扩大了肿瘤疫苗的范围,从而大幅增强了不同肿瘤疫苗的免疫效果。合成生物学的快速发展将加速对肿瘤疫苗的实验研究进度,最终导致临床治疗效果的持续增强。

关键词: 肿瘤疫苗, 新抗原, 树突状细胞, 细胞疫苗, 合成生物学

Abstract:

The central dogma of biology, which delineates the flow of genetic information from DNA to RNA to protein, along with the principles of cellular immunology, provides a foundational understanding for harnessing the power of synthetic biology to combat cancer. The application of synthetic biology in the design and production of novel tumor vaccines marks a pivotal advance in the field of cancer immunotherapy. This study delves into the cutting-edge development in the creation of therapeutic tumor vaccines, with a particular focus on two critical components: antigen selection and vaccine design. The request for more precise and effective tumor vaccines has garnered the attention of researchers globally. These vaccines are designed to target tumor-specific antigens or those related to tumor growth and survival pathways. Traditional approaches to antigen selection have typically involved targeting specific genes with tumors. However, the advent of high-throughput sequencing and mass spectrometry has revolutionized this process by enabling the screening of novel antigens, thereby enhancing the precision and immunogenicity of vaccines. In recent years, the landscape of tumor vaccines has been significantly broadened by the engineering of vaccines through various platforms. These include DNA-based vaccines, mRNA vaccines, viral or bacterial vector vaccines, and cell-based vaccines. These innovative approaches offer a stark contrast to traditional peptide vaccines, significantly amplifying the immune response against a variety of tumor types. The versatility of synthetic biology allows for the customization of vaccines to target a wide array of tumor antigens, thereby potentiating a more robust and targeted immune reaction. The progress made in synthetic biology is not only refining existing vaccine strategies but also accelerating the pace of experimental research in tumor vaccines. This rapid advancement holds the promise of continually improving the clinical therapeutic effects of these vaccines. As researchers continue to unravel the complexities of tumor immunology and synthetic biology techniques become more efficient, the intersection of these fields is expected to yield a new generation of tumor vaccines that are not only more effective but also safer and more accessible to patients. In conclusion, the integration of biological knowledge and technological innovation in synthetic biology is transforming the development of tumor vaccines. The focus on optimizing antigen selection and vaccine design is driving the creation of more potent and tailored immunotherapies. It is anticipated that synthetic biology will play an even greater role in enhancing the efficacy of tumor vaccines, offering cancer patients with hope in the ongoing battle against this devastating disease. {L-End}

Key words: cancer vaccine, neoantigen, dendritic cell, DC vaccine, biosynthesis

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