Nanobody Engineered and Photosensitiser Loaded Bacterial Outer Membrane Vesicles Potentiate Antitumour Immunity and Immunotherapy
Bacterial outer membrane vesicles (OMVs) are promising as antitumour agents, but their clinical application is limited by toxicity concerns and unclear mechanisms. We engineered OMVs with cadherin 17 (CDH17) tumour-targeting nanobodies, enhancing tumour selectivity and efficacy while reducing adverse effects. These engineered OMVs function as natural stimulator of interferon genes (STING) agonists, activating the cyclic GMP-AMP synthase (cGAS)-STING pathway in cancer cells and tumour-associated macrophages (TAMs). Loading engineered OMVs with photoimmunotherapy photosensitisers further enhanced tumour inhibition and STING activation in TAMs. Combining nanobody-engineered OMV-mediated photoimmunotherapy with CD47 blockade effectively suppressed primary and metastatic tumours, establishing sustained antitumour immune memory. This study demonstrates the potential of nanobody-engineered OMVs as STING agonists and provides insights into novel OMV-based immunotherapeutic strategies harnessing the innate immune system against cancer. Our findings open new avenues for OMV applications in tumour immunotherapy, offering a promising approach to overcome current limitations in cancer treatment.
Authors
- Yufeng Yuan (ORCID: https://orcid.org/0000-0003-3924-3803)
- Xiaolong Xu (ORCID: https://orcid.org/0000-0003-3333-0906)
- Tianyu Zhong (ORCID: https://orcid.org/0000-0003-1934-0032)
- Rui Hou (ORCID: https://orcid.org/0000-0001-6571-1514)
- Chengming Qu (ORCID: https://orcid.org/0000-0002-9773-8815)
- Peng Xia (ORCID: https://orcid.org/0000-0003-3891-3385)
- Felix Rückert (ORCID: https://orcid.org/0000-0003-0301-8479)
- Zhijie Li (ORCID: https://orcid.org/0000-0002-5445-7976)
- Jigang Wang (ORCID: https://orcid.org/0000-0002-0575-0105)
- Liang Zhao (ORCID: https://orcid.org/0000-0002-1429-0884)
- Ming Tian (ORCID: https://orcid.org/0000-0003-4014-7392)
- Jingbo Ma (ORCID: https://orcid.org/0000-0003-0101-0318)
- Zhifen Li
- Han Li (ORCID: https://orcid.org/0009-0003-6884-2714)
Institutions
- Jinan University (CN)
- Henan University (CN)
- The University of Western Australia (AU)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Fudan University (CN)
- Harry Perkins Institute of Medical Research (AU)
- Southern University of Science and Technology (CN)
- Wuhan University (CN)
- University of Chicago (US)
- Queen Elizabeth II Medical Centre (AU)
- Huadong Hospital (CN)
- Nanfang Hospital (CN)
- Zhongnan Hospital of Wuhan University (CN)
- Diakonissenkrankenhaus (DE)
- Shanxi Datong University (CN)
- Southern Medical University (CN)
Publication Details
- Journal
- Journal of Extracellular Vesicles
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1002/jev2.70069
- Citations
- 12
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 9.57
Funders
- Postdoctoral Science Foundation of Hubei Province
- Shenzhen Technology University
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- China Academy of Chinese Medical Sciences
- Wuhan University
- Shenzhen Municipal Science and Technology Innovation Council
- Zhongnan Hospital of Wuhan University
- National Postdoctoral Program for Innovative Talents
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities
- Basic and Applied Basic Research Foundation of Guangdong Province