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Published on: July 25, 2022
Nanobody Engineered and Photosensitiser Loaded Bacterial Outer Membrane Vesicles Potentiate Antitumour Immunity and
Peng Xia1,2,3, Chengming Qu1, Xiaolong Xu2
1Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan University, Wuhan, Hubei, P. R. China.
Abstract:
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.
Insights
Engineered bacterial outer membrane vesicles (OMVs) target tumors, activate anti-cancer STING pathways, and enhance immunotherapy. This approach reduces toxicity and establishes lasting immune memory against cancer.
Area of Science:
- Immunology
- Nanotechnology
- Oncology
Background:
- Bacterial outer membrane vesicles (OMVs) show potential as antitumour agents but face limitations due to toxicity and unclear mechanisms.
- Engineering OMVs can improve their therapeutic properties and target specificity.
Purpose of the Study:
- To engineer OMVs with tumor-targeting nanobodies and evaluate their efficacy as STING agonists for cancer immunotherapy.
- To investigate the combination of nanobody-engineered OMVs with photoimmunotherapy and CD47 blockade for enhanced antitumour effects.
Main Methods:
- Engineered OMVs with cadherin 17 (CDH17) tumor-targeting nanobodies.
- Assessed STING pathway activation in cancer cells and tumor-associated macrophages (TAMs).
- Combined nanobody-engineered OMVs with photoimmunotherapy and CD47 blockade.
Main Results:
- Engineered OMVs demonstrated enhanced tumor selectivity and reduced toxicity.
- OMVs effectively activated the cyclic GMP-AMP synthase (cGAS)-STING pathway.
- Combination therapy led to significant suppression of primary and metastatic tumors and established immune memory.
Conclusions:
- Nanobody-engineered OMVs are potent STING agonists with potential for cancer immunotherapy.
- This approach offers a novel strategy to harness the innate immune system against cancer.
- Findings pave the way for advanced OMV-based immunotherapies to overcome current cancer treatment limitations.
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