中文版 | English
题名

Nanobody-Engineered Biohybrid Bacteria Targeting Gastrointestinal Cancers Induce Robust STING-Mediated Anti-Tumor Immunity

作者
通讯作者Li, Zhijie; Liang, Zhen; Wang, Jigang
发表日期
2024
DOI
发表期刊
EISSN
2198-3844
摘要
Bacteria can be utilized for cancer therapy owing to their preferential colonization at tumor sites. However, unmodified non-pathogenic bacteria carry potential risks due to their non-specific targeting effects, and their anti-tumor activity is limited when used as monotherapy. In this study, a biohybrid-engineered bacterial system comprising non-pathogenic MG1655 bacteria modified with CDH17 nanobodies on their surface and conjugated with photosensitizer croconium (CR) molecules is developed. The resultant biohybrid bacteria can efficiently home to CDH17-positive tumors, including gastric, pancreatic, and colorectal cancers, and significantly suppress tumor growth upon irradiation. More importantly, biohybrid bacteria-mediated photothermal therapy (PTT) induced abundant macrophage infiltration in a syngeneic murine colorectal model. Further, that the STING pathway is activated in tumor macrophages by the released bacterial nucleic acid after PTT is revealed, leading to the production of type I interferons. The addition of CD47 nanobody but not PD-1 antibody to the PTT regimen can eradicate the tumors and extend survival. This results indicate that bacteria endowed with tumor-specific selectivity and coupled with photothermal payloads can serve as an innovative strategy for low-immunogenicity cancers. This strategy can potentially reprogram the tumor microenvironment by inducing macrophage infiltration and enhancing the efficacy of immunotherapy targeting macrophages.
© 2024 The Author(s). Advanced Science published by Wiley-VCH GmbH.
收录类别
EI ; SCI
语种
英语
学校署名
第一 ; 通讯
资助项目
X.X. and Y.D. contributed equally to this work. This work was supported by the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences (CI2023D003, CI2021B014), the Science and Technology Foundation of Shenzhen (JCYJ20210324115800001; JCYJ20210324113608023; JCYJ20200109120205924), the National Key Research and Development Program of China (2022YFC2303600 and 2020YFA0908000), the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No: ZYYCXTD\u2010C\u2010202002), the CACMS Innovation Fund (CI2023E002, CI2021A05101 and CI2021A05104), the Science and Technology Foundation of Shenzhen (Shenzhen Clinical Medical Research Center for Geriatric Diseases), the Shenzhen Medical Research Fund (B2302051), the Distinguished Expert Project of Sichuan Province Tianfu Scholar (CW202002), the Fundamental Research Funds for the Central public welfare research institutes (ZZ16\u2010ND\u201010\u201023, ZZ15\u2010ND\u201010, ZZ14\u2010ND\u2010010, ZZ14\u2010FL\u2010002, ZZ14\u2010YQ\u2010050, ZZ14\u2010YQ\u2010051), the Shenzhen Science and Technology Innovation Commission (JCYJ20200109120205924), GuangDong Basic and Applied Basic Research Foundation (2021A1515012164; 2022A1515110745; 2021A1515111188), the Shenzhen Science and Technology Innovation Committee (SZSTI) (RCYX20221008092950121), the National Natural Science Foundation of China (82373775; 82070517; 82170842; 8230130506; 82371572), the HUILAN Public Welfare, International Science and Technology Cooperation for Shenzhen Technology Innovation Plan (GJHZ20200731095411034), Chinese Postdoctoral Science Foundation (2022M711328) and Shenzhen People's Hospital grant (SYWGSCGZH202304).
出版者
EI入藏号
20242516281572
EI主题词
Diseases ; Macrophages ; Nucleic acids ; Photosensitizers ; Tumors
EI分类号
Biological Materials and Tissue Engineering:461.2 ; Immunology:461.9.1 ; Light/Optics:741.1 ; Biochemistry:801.2 ; Organic Compounds:804.1
来源库
EV Compendex
引用统计
被引频次[WOS]:2
成果类型期刊论文
条目标识符http://sustech.caswiz.com/handle/2SGJ60CL/794633
专题南方科技大学第一附属医院
南方科技大学
作者单位
1.Department of Geriatrics and Shenzhen Clinical Research Centre for Geriatrics, Department of Urology, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology, The Second Clinical Medical College, Jinan University), Guangdong, Shenzhen; 518020, China
2.Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou; 510632, China
3.Department of Medical Imaging, The Third Affiliated Hospital, Southern Medical University (Academy of Orthopedics Guangdong Province), Guangzhou; 510515, China
4.Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Hubei, Wuhan; 430071, China
5.Department of Pathology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan; 528308, China
6.Department of Pathology & Guangdong Province Key Laboratory of Molecular Tumor Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou; 510515, China
7.Department of Oncology, The Affiliated Hospital of Southwest Medical University, Sichuan, Luzhou; 646000, China
8.Department of Traditional Chinese Medicine and School of Pharmaceutical Sciences, Southern Medical University, Guangzhou; 510515, China
9.State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing; 100700, China
10.State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng; 475004, China
第一作者单位南方科技大学第一附属医院
通讯作者单位南方科技大学第一附属医院
第一作者的第一单位南方科技大学第一附属医院
推荐引用方式
GB/T 7714
Xu, Xiaolong,Ding, Youbin,Dong, Yafang,et al. Nanobody-Engineered Biohybrid Bacteria Targeting Gastrointestinal Cancers Induce Robust STING-Mediated Anti-Tumor Immunity[J]. Advanced Science,2024.
APA
Xu, Xiaolong.,Ding, Youbin.,Dong, Yafang.,Yuan, Haitao.,Xia, Peng.,...&Wang, Jigang.(2024).Nanobody-Engineered Biohybrid Bacteria Targeting Gastrointestinal Cancers Induce Robust STING-Mediated Anti-Tumor Immunity.Advanced Science.
MLA
Xu, Xiaolong,et al."Nanobody-Engineered Biohybrid Bacteria Targeting Gastrointestinal Cancers Induce Robust STING-Mediated Anti-Tumor Immunity".Advanced Science (2024).
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