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Due to the vascular network and immunosuppressive microenvironment of the lungs, lung metastasis poses a challenge in cancer treatment. Traditional subcutaneous vaccines usually fail to elicit local immune responses at metastatic sites. To address this, bacterial membrane vesicles expressing ClyA-OVA257-264 from engineered Escherichia coli were used to develop an inhalable nanovaccine, BMVax (bacterial membrane-based vaccine). Proteomics that preserved the immune-stimulating membrane proteins enabled efficient co-delivery of antigens. BMVax ensured antigen cross-presentation (increased 2.2-fold compared to antigen BMV combinations), driving robust antigen-specific T cell proliferation.Inhalation can trigger a strong immune response in the tracheobronchial lymph nodes, enhancing germinal center B cells (≈5.8-fold), follicular helper T cells (≈4.9-fold), and mature dendritic cells (≈2.5-fold), achieving an 83.3% prevention rate of lung metastasis. In the B16-OVA lung metastasis model, inhaled BMVax is superior to subcutaneous administration in tumor suppression. It can double the number of germinal center B cells in lymph nodes, increase follicular helper T cells by 2.9-fold, and raise the number of antigen-specific T cells in lung tissue by 2.9 times compared to subcutaneous immunization. Tumor-infiltrating T cells exhibit enhanced cytotoxicity and proliferative ability, strengthening their therapeutic advantage over subcutaneous immunization. These findings highlight the potential of BMVax as an inhalable cancer vaccine, capable of eliciting a strong immune response and effectively combating pulmonary metastatic malignancies.
Summary
The lungs are a major site for metastasis of various cancers, but traditional subcutaneous vaccines struggle to induce local immune responses in the lungs. To address this issue, researchers have developed an inhalable nanovaccine based on engineered bacterial membrane vesicles—BMVax. It expresses the ClyA-OVA antigen through genetically engineered Escherichia coli, forming membrane vesicles with uniform nanoscale size and good stability, effectively retaining immunostimulatory proteins and antigens.
In animal experiments, inhalation of BMVax can significantly activate immune cells in the tracheobronchial lymph nodes, including germinal center B cells, follicular helper T cells, and mature dendritic cells, and greatly increase the number of antigen-specific T cells in lung tissue. In a melanoma lung metastasis model, BMVax demonstrated excellent preventive and therapeutic effects, achieving an 83.3% complete prevention rate, significantly better than subcutaneous injection. This vaccine can not only induce a strong local immune response but also promote systemic immune memory, providing a new strategy for developing inhalable cancer vaccines targeting lung metastases.
References:
DOI: 10.1002/adma.202506174
