Mucinase-engineered cell membrane nanovesicles degrade the glycocalyx shield to potentiate antitumor immunity - PubMed
3 days ago
- #Cancer Immunotherapy
- #Glycocalyx Engineering
- #Nanovesicles
- The tumor glycocalyx forms a protective shield that masks checkpoint proteins and reduces immunotherapy efficacy.
- Bacterial protease StcE can degrade the glycocalyx by cleaving mucin domains, but faces off-target toxicity and high immunogenicity.
- Researchers developed mucinase-engineered cell membrane fusion nanovesicles (FNVs) codisplaying StcE and CD47 nanobodies (nCD47) for controlled glycocalyx degradation.
- StcE-nCD47-FNVs retained mucin-hydrolyzing activity and enhanced nCD47 binding to CD47 on tumor cells, boosting antitumor immune responses.
- The platform showed superior tumor accumulation, biosafety, and prolonged circulation compared to free StcE, reducing off-target effects.
- In murine colorectal and breast cancer models, StcE-nCD47-FNVs suppressed tumor growth and metastasis by remodeling the tumor microenvironment.
- This approach increases M1 macrophage polarization and CD8+ T cell infiltration, offering a safe and versatile strategy for cancer immunotherapy.