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Nanobody engineered and photosensitiser loaded bacterial outer membrane vesicles potentiate anti-tumor immunity and immunotherapy

ABSTRACT: Bacterial outer membrane vesicles (OMVs) are promising as antitumor agents, but their clinical application is limited by toxicity concerns and unclear mechanisms. We engineered OMVs with CDH17 tumor-targeting nanobodies, enhancing tumor 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 tumor-associated macrophages (TAMs). Loading engineered OMVs with photoimmunotherapy photosensitizers further enhanced tumor inhibition and STING activation in TAMs. Combining nanobody-engineered OMV-mediated photoimmunotherapy with CD47 blockade effectively suppressed primary and metastatic tumors, establishing sustained antitumor 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 tumor immunotherapy, offering a promising approach to overcome current limitations in cancer treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE272295 | GEO | 2025/03/28

REPOSITORIES: GEO

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