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journal article·2024-08Open access

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

Xiaolong Xu, Youbin Ding, Yafang Dong, Haitao Yuan, Peng Xia, Chengming Qu, Jingbo Ma, Huifang Wang, Xiaodong Zhang, Liang Zhao, Zhijie Li, Zhen Liang, Jigang Wang

Advanced Science· Volume 11· Issue 31
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Source abstract

Abstract

Abstract 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.
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Research context

Nanomaterials

OpenAlex topics: Cancer Research and Treatments · Nanoplatforms for cancer theranostics · Bacteriophages and microbial interactions

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

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) Shenzhen Guangdong 518020 China

Integrated Chinese and Western Medicine Postdoctoral Research Station Jinan University Guangzhou 510632 China

Department of Medical Imaging The Third Affiliated Hospital Southern Medical University (Academy of Orthopedics Guangdong Province) Guangzhou 510515 China

Department of Hepatobiliary & Pancreatic Surgery Zhongnan Hospital of Wuhan University Wuhan Hubei 430071 China

Department of Pathology Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde) Foshan 528308 China

Department of Pathology & Guangdong Province Key Laboratory of Molecular Tumor Pathology, School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China

Department of Oncology The Affiliated Hospital of Southwest Medical University Luzhou Sichuan 646000 China

Department of Traditional Chinese Medicine and School of Pharmaceutical Sciences Southern Medical University Guangzhou 510515 China

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

State Key Laboratory of Antiviral Drugs School of Pharmacy Henan University Kaifeng 475004 China

Funding

National Key Research and Development Program of China · Science, Technology and Innovation Commission of Shenzhen Municipality · National Natural Science Foundation of China · China Postdoctoral Science Foundation

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