Antitumor Immunity Mediated by Nanoreactors Based on Bacterial Membrane Vesicles

Area of Science:

• Oncology
• Immunology
• Biotechnology

Background:

• Traditional cancer vaccines face challenges including low immunogenicity, complex manufacturing, and safety issues, limiting their clinical use.
• There is a critical need for advanced cancer vaccines that offer high efficacy and good tolerability.
• Multifunctional vaccine platforms are required to overcome the limitations of current cancer immunotherapies.

Purpose of the Study:

• To develop and evaluate a novel tumor vaccine platform utilizing engineered bacterial membrane vesicles (E-MVs).
• To assess the potential of E-MVs displaying MUC1 VNTR antigen for both therapeutic and prophylactic antitumor immunity.
• To investigate the immunogenicity and efficacy of E-MV-based vaccines in preclinical cancer models.

Main Methods:

• Engineered bacterial membrane vesicles (E-MVs) were produced from *Escherichia coli* Rosetta (DE3) and loaded with the MUC1 VNTR tumor antigen.
• E-MVs were characterized for morphology and size distribution (100-200 nm).
• Subcutaneous administration in mouse models assessed E-MV biodistribution, immune cell uptake, T cell activation, and antitumor effects in cold and hot tumors.

Main Results:

• E-MVs efficiently accumulated in draining lymph nodes and were internalized by dendritic cells, promoting T cell cross-presentation.
• E-MV vaccination induced significant CD8+ T cell infiltration and IFN-γ production, leading to potent antitumor immune responses.
• The E-MV vaccine suppressed tumor growth, prolonged survival, and provided protection against tumor challenge in breast and melanoma models.

Conclusions:

• Engineered bacterial membrane vesicles (E-MVs) represent a versatile and potent platform for cancer vaccines.
• This E-MV platform integrates antigen delivery with intrinsic adjuvant properties, enabling both therapeutic and prophylactic antitumor immunity.
• The E-MV vaccine strategy is simple, efficient, and shows promise for clinical translation in inducing durable antitumor immunity.