合成生物学在基于微生物载体肿瘤疫苗设计中的应用

谭子斌; 梁康; 陈有海

doi:10.12211/2096-8280.2023-079

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合成生物学在基于微生物载体肿瘤疫苗设计中的应用

特约评述 | 更新时间：2025-03-20

- 合成生物学在基于微生物载体肿瘤疫苗设计中的应用
- Applications of synthetic biology in developing microbial-vectored cancer vaccines
- 合成生物学 2024年5卷第2期页码：221-238
- 作者机构：
  
  深圳理工大学药学院，中国科学院深圳先进技术研究院癌症免疫中心，广东深圳 518055
- 作者简介：
  
  [ "谭子斌（1990—），男，助理研究员。研究方向为肿瘤疫苗与免疫治疗。E-mail：tanzibin108@gmail.com" ]
  [ "陈有海（1963—），博士生导师，欧洲科学院（Academia Europaea）院士，美国医学与生物工程院（AIMBE）Fellow，国家特聘教授，教育部长江学者，深圳理工大学药学院讲席教授、院长。研究方向为肿瘤免疫治疗。E-mail：yh.chen@siat.ac.cn" ]
- 基金信息：
  
  国家重点研发计划(2022YFA0912400);深圳市科技计划(JCYJ20220818100806015);国家自然科学基金(32130040;82250710172);深圳市医学科研基金(B2301006)
- DOI：10.12211/2096-8280.2023-079
  中图分类号： R730.3
- 收稿：2023-11-20，
  
  修回：2024-02-05，
  
  纸质出版：2024-04-30
- 稿件说明：
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谭子斌，梁康，陈有海. 合成生物学在基于微生物载体肿瘤疫苗设计中的应用［J］. 合成生物学， 2024， 5（2）： 221-238

TAN Zibin， LIANG Kang， CHEN Youhai. Applications of synthetic biology in developing microbial-vectored cancer vaccines［J］. Synthetic Biology Journal， 2024， 5（2）： 221-238
谭子斌，梁康，陈有海. 合成生物学在基于微生物载体肿瘤疫苗设计中的应用［J］. 合成生物学， 2024， 5（2）： 221-238 DOI： 10.12211/2096-8280.2023-079.

TAN Zibin， LIANG Kang， CHEN Youhai. Applications of synthetic biology in developing microbial-vectored cancer vaccines［J］. Synthetic Biology Journal， 2024， 5（2）： 221-238 DOI： 10.12211/2096-8280.2023-079.

摘要

合成生物学有望创造具备独特优势的抗肿瘤微生物疫苗，合成生物学改造的微生物更能适应肿瘤微环境并在其中富集与增殖，削弱或者逆转免疫抑制细胞的功能，并增强肿瘤抗原的呈递，诱发多种先天与适应性抗肿瘤免疫反应，所以合成生物学已成为肿瘤疫苗研究的重要工具。本文总结了合成生物学在细菌和病毒载体肿瘤疫苗开发中的几个关键应用，其中包括减弱微生物载体毒性的方法，例如去除、失活或修改其致病基因等。讨论了增强它们在肿瘤组织中的趋向性和适应性的策略，如改变它们的细胞入侵分子或引入环境控制的基因表达系统等；也讨论了降低全身毒性的方法。为了充分利用微生物复制引起的肿瘤微环境改变的潜力，多种合成生物学手段被用于改造微生物载体，这些方法包括将外源基因引入微生物基因组，使其生产诸如细胞因子、趋化因子或单克隆抗体等分子，这些分子可以增强先天和适应性免疫细胞的招募和激活，促进肿瘤细胞免疫原性死亡，并增强肿瘤相关抗原的呈递。此外，还探讨了将肿瘤抗原引入载体中的方法，例如不同的装载方式、位置和释放机制。开发微生物载体肿瘤疫苗存在重大挑战，包括安全性问题、抗载体免疫与抗肿瘤免疫的复杂关系和肿瘤生物学的复杂性，克服这些困难将成为未来研究的重要方向。

Abstract

The development of cancer vaccines is confronted with significant challenges. Synthetic biology emerges as a potent tool for addressing these challenges

due to its ability to modify and engineer microbes capable of adapting to and colonizing on tumor tissues to change the immunosuppressive tumor microenvironments

augment antigen presentations

and stimulate both innate and adaptive immune responses against tumors

in situ

. This review comments on several pivotal applications of synthetic biology in engineering bacterial and viral vectored cancer vaccines. We start with discussion on methods to mitigate the pathogenicity of bacterial or viral vectors

including the removal

deactivation

or modification of their virulent genes. Furthermore

we address strategies for enhancing their tropism and fitness within tumor tissues

such as the alteration of their cellular entry proteins or the implementation of environmentally controlled gene expression systems. Approaches to minimize their systemic toxicity are also described. To fully harness the potential of tumor microenvironment modifications induced by microbial replication

we underscore studies employing synthetic biology methods

which involve the introduction of foreign genes into the microbial genomes

thereby enabling the production of agents like cytokines

chemokines

or monoclonal antibodies to enhance the recruitment and activation of innate and adaptive cells

promote immunogenic cell death

and augment the presentation of tumor-associated antigens. We also delve into the applic

ations of synthetic biology for the introduction of tumor antigens to the vectors

discussing various loading methods

locations

and releasing mechanisms to generate an optimized tumor-specific immune response. At the end

we highlight substantial challenges that arise in the development of microbial vectored cancer vaccines

including safety considerations

intricate interactions between anti-vector and anti-tumor immunity

and the inherent complexity of tumor biology

and propose strategies for addressing these obstacles. In conclusion

this review emphasizes the crucial role of synthetic biology in the engineering of microbes

which is instrumental in advancing the development of cancer vaccines.

关键词

Keywords

references

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