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  2. 上海药物研究所
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  4. 新药研究国家重点实验室
Fine-tuning Bacterial Cyclic di-AMP Production for Durable Antitumor Effects Through the Activation of the STING Pathway

文献类型：期刊论文

作者Jiang, Yu1,6,7; Li, Xiyuan2,3,4; Qian, Fenghui1,5; Sun, Bingbing5; Wang, Xiyuan2; Zhang, Yan2; Zhang, Deqiang2; Geng, Meiyu2,3,4; Xie, Zuoquan2,4; Yang, Sheng1,5,6
刊名RESEARCH
出版日期2023-02-21
卷号6页码:15
ISSN号2096-5168
DOI10.34133/research.0102
通讯作者Xie, Zuoquan(zqxie@simm.ac.cn) ; Yang, Sheng(syang@sibs.ac.cn)
英文摘要The stimulator of interferon genes (STING) protein is an important and promising innate immune target for tumor therapy. However, the instability of the agonists of STING and their tendency to cause systemic immune activation is a hurdle. The STING activator, cyclic di-adenosine monophosphate (CDA), produced by the modified Escherichia coli Nissle 1917, shows high antitumor activity and effectively reduces the systemic effects of the "off-target" caused by the activation of the STING pathway. In this study, we used synthetic biological approaches to optimize the translation levels of the diadenylate cyclase that catalyzes CDA synthesis in vitro. We developed 2 engineered strains, CIBT4523 and CIBT4712, for producing high levels of CDA while keeping their concentrations within a range that did not compromise the growth. Although CIBT4712 exhibited stronger induction of the STING pathway corresponding to in vitro CDA levels, it had lower antitumor activity than CIBT4523 in an allograft tumor model, which might be related to the stability of the surviving bacteria in the tumor tissue. CIBT4523 exhibited complete tumor regression, prolonged survival of mice, and rejection of rechallenged tumors, thus, offering new possibilities for more effective tumor therapy. We showed that the appropriate production of CDA in engineered bacterial strains is essential for balancing antitumor efficacy and self-toxicity.
WOS关键词ESCHERICHIA-COLI NISSLE-1917 ; DNA SENSOR ; COLONIZATION ; INFLAMMATION ; INDUCTION ; MECHANISM ; CYTOKINES ; CELL ; CSF
资助项目National Natural Science Foundation of China[21825804] ; National Science and Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002019] ; Shanghai Municipal Science and Technology Major Project ; Lingang Laboratory[LG2021030208] ; Natural Science Foundation of China for Innovation Research Group[81821005] ; Collaborative Innovation Cluster Project of Shanghai Municipal Commission of Health and Family Planning[2020CXJQ02]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000994210600002
出版者AMER ASSOC ADVANCEMENT SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/306629]  
专题新药研究国家重点实验室
通讯作者Xie, Zuoquan; Yang, Sheng
作者单位1.Shanghai Res & Dev Ctr Ind Biotechnol, Shanghai, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
4.Univ Chinese Acad Sci, Beijing, Peoples R China
5.Chinese Acad Sci, CAS Ctr Excellence Mol Plant Sci, Key Lab Synthet Biol, Shanghai, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Biol Sci, Huzhou Res Ctr Ind Biotechnol, Huzhou, Peoples R China
7.Shanghai Taoyusheng Biotechol Co Ltd, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Jiang, Yu,Li, Xiyuan,Qian, Fenghui,et al. Fine-tuning Bacterial Cyclic di-AMP Production for Durable Antitumor Effects Through the Activation of the STING Pathway[J]. RESEARCH,2023,6:15.
APA Jiang, Yu.,Li, Xiyuan.,Qian, Fenghui.,Sun, Bingbing.,Wang, Xiyuan.,...&Yang, Sheng.(2023).Fine-tuning Bacterial Cyclic di-AMP Production for Durable Antitumor Effects Through the Activation of the STING Pathway.RESEARCH,6,15.
MLA Jiang, Yu,et al."Fine-tuning Bacterial Cyclic di-AMP Production for Durable Antitumor Effects Through the Activation of the STING Pathway".RESEARCH 6(2023):15.

入库方式： OAI收割

来源：上海药物研究所

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