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Updated: May 16, 2026

Preparation, Characteristics, Toxicity, and Efficacy Evaluation of the Nasal Self-Assembled Nanoemulsion Tumor Vaccine In Vitro and In Vivo
Published on: September 28, 2022
Mucinase-engineered cell membrane nanovesicles degrade the glycocalyx shield to potentiate antitumor immunity
Xiaorui Geng1, Silan Liu1,2,3, Yuanwei Pan1
1Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518132, China.
Abstract:
The tumor glycocalyx forms a protective shield that masks checkpoint proteins and compromises the efficacy of immunotherapies. While the bacterial protease StcE can degrade this barrier by cleaving O-glycosylated mucin domains, its therapeutic potential is hindered by off-target toxicity and high immunogenicity. To overcome these limitations, we developed a biomimetic platform of cell membrane fusion nanovesicles (FNVs) that codisplay StcE and CD47 nanobodies (nCD47) for spatially controlled glycocalyx degradation and enhanced checkpoint blockade. Using the SpyTag/SpyCatcher system, we generated StcE-displaying NVs, which were then fused with nCD47-displaying NVs. The resulting StcE-nCD47-FNVs retained potent mucin-hydrolyzing activity and exhibited well-defined physicochemical properties. By removing the mucin barrier, StcE-nCD47-FNVs significantly enhanced nCD47 binding to CD47 on tumor cells, thereby potentiating antitumor immune responses. More importantly, benefiting from prolonged circulation of FNVs and tumor targeting of nCD47, the StcE-nCD47-FNV platform demonstrated superior tumor accumulation and biosafety compared to free StcE. In murine models of colorectal and breast cancer, StcE-nCD47-FNVs significantly suppressed tumor growth and metastasis by remodeling the tumor microenvironment, as evidenced by increased M1 macrophage polarization and CD8+ T cell infiltration. By integrating glycocalyx engineering with vesicle nanotechnology, StcE-nCD47-FNVs offer a safe, robust, and versatile strategy to breach the tumor glycocalyx for next-generation cancer immunotherapy.
Insights
This study introduces fusion nanovesicles (FNVs) that degrade the tumor glycocalyx, enhancing cancer immunotherapy efficacy. These StcE-nCD47-FNVs improve tumor targeting and reduce toxicity for better immune responses.
Area of Science:
- Biotechnology
- Immunology
- Nanomedicine
Background:
- The tumor glycocalyx shields tumors from immunotherapy by masking checkpoint proteins.
- Bacterial protease StcE degrades the glycocalyx but has toxicity and immunogenicity issues.
- Existing immunotherapies face challenges due to the protective tumor microenvironment.
Purpose of the Study:
- To develop a novel biomimetic platform for targeted glycocalyx degradation and enhanced cancer immunotherapy.
- To overcome the limitations of free StcE by creating a safer and more effective delivery system.
- To investigate the therapeutic potential of StcE-nCD47-FNVs in preclinical cancer models.
Main Methods:
- Engineered cell membrane fusion nanovesicles (FNVs) to co-display StcE and CD47 nanobodies (nCD47) using the SpyTag/SpyCatcher system.
- Characterized the physicochemical properties and mucin-hydrolyzing activity of the resulting StcE-nCD47-FNVs.
- Evaluated the efficacy of StcE-nCD47-FNVs in murine models of colorectal and breast cancer, assessing tumor growth, metastasis, and immune cell infiltration.
Main Results:
- StcE-nCD47-FNVs demonstrated potent mucin degradation and enhanced nCD47 binding to tumor cells.
- The FNV platform exhibited prolonged circulation, improved tumor accumulation, and better biosafety compared to free StcE.
- Significant suppression of tumor growth and metastasis was observed, accompanied by M1 macrophage polarization and increased CD8+ T cell infiltration.
Conclusions:
- StcE-nCD47-FNVs represent a safe, robust, and versatile strategy for breaching the tumor glycocalyx.
- This integrated approach of glycocalyx engineering and vesicle nanotechnology enhances checkpoint blockade immunotherapy.
- The developed platform holds promise for next-generation cancer immunotherapies by remodeling the tumor microenvironment.
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