Modified Bacterial Outer Membrane Vesicles Induce Autoantibodies for Tumor Therapy

Abstract

Using monoclonal antibodies to block tumor angiogenesis has yielded effective antitumor effects. However, this treatment method has long cycles and is very expensive; therefore, its long-term and extensive application is limited. In this study, we developed a nanovaccine using bacterial biomembranes as carriers for antitumor therapy. The whole basic fibroblast growth factor (BFGF) molecule (154 amino acids (aa)) was loaded onto bacterial outer membrane vesicles (OMVs) using gene recombination technology. The strong adjuvant effect of OMVs was used to induce the host to produce anti-BFGF autoantibodies. We proved that persistent anti-BFGF autoantibodies can be induced in mice after only 3 immunizations to antagonize BFGF functions. The effects included multiple tumor suppression functions, including inhibition of tumor angiogenesis, induction of tumor cell apoptosis, reversal of tumor immune barriers, and promotion of tumor-specific cytotoxic T lymphocytes (CTLs), eventually causing tumor regression. We confirmed that bacterial biomembranes can be used as a vaccine delivery system to induce the production of antibodies against autoantigens, which may be used for tumor therapy. This study expands the application fields of bacterial biomembrane systems and provides insight for tumor immunotherapy other than monoclonal antibody technology.