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Engineered Outer Membrane Vesicles as Nanosized Immune Cell Engagers for Enhanced Solid Tumor Immunotherapy
Jianan Sun1, Liu Tan1, Bang-Ce Ye2
1Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P. R. China.
ACS Nano
|October 25, 2024
Summary
Researchers developed a novel OMV-based immune cell engager (OMV-NICE) for solid tumor immunotherapy. This dual-targeting approach enhances immune cell engagement and demonstrates superior antitumor activity in preclinical models.
Area of Science:
- Immunology
- Biotechnology
- Nanomedicine
Background:
- Solid tumors present significant challenges for current tumor immunotherapies.
- Developing effective strategies to engage immune cells against solid tumors is crucial.
Purpose of the Study:
- To engineer an OMV-based nanosized immune cell engager (OMV-NICE) for enhanced solid tumor immunotherapy.
- To investigate the dual-targeting capabilities of OMV-NICE against CD47/SIRPα and PD-1/PD-L1 pathways.
Main Methods:
- Utilized bacterial outer membrane vesicles (OMVs) as scaffolds for nanobody conjugation.
- Employed orthogonal SpyCatcher-SpyTag and SnoopCatcher-SnoopTag chemistries for dual and trivalent nanobody attachment.
- Evaluated OMV-NICE efficacy through in vitro assays (macrophage phagocytosis, T cell cytotoxicity) and in vivo studies in a B16-F10 melanoma mouse model.
Main Results:
- Confirmed functional retention of nanobodies on OMV-NICE, showing synergistic enhancement of immune cell functions.
- Demonstrated superior in vivo antitumor activity of OMV-NICE compared to unconjugated nanobodies and OMVs alone.
- Mechanistic studies revealed enhanced recruitment of macrophages and T cells to the tumor site by OMV-NICE.
Conclusions:
- The developed OMV-NICE platform offers a promising new approach for solid tumor immunotherapy.
- OMV-NICE effectively engages immune cells and exhibits potent antitumor effects, expanding the repertoire of immune cell engagers.
