Anti-Tumor Efficacy of In Situ Vaccination Using Bacterial Outer Membrane Vesicles

Abstract

In situ vaccination (ISV) is a promising cancer immunotherapy strategy that consists of the intratumoral administration of immunostimulatory molecules (adjuvants). The rationale is that tumor antigens are abundant at the tumor site, and therefore, to elicit an effective anti-tumor immune response, all that is needed is an adjuvant, which can turn the immunosuppressive environment into an immunologically active one. Bacterial outer membrane vesicles (OMVs) are potent adjuvants since they contain several microbe-associated molecular patterns (MAMPs) naturally present in the outer membrane and in the periplasmic space of Gram-negative bacteria. Therefore, they appear particularly indicted for ISV. In this work, we first show that the OMVs from E. coli BL21(DE3)Δ60 strain promote a strong anti-tumor activity when intratumorally injected into the tumors of three different mouse models. Tumor inhibition correlates with a rapid infiltration of DCs and NK cells. We also show that the addition of neo-epitopes to OMVs synergizes with the vesicle adjuvanticity, as judged by a two-tumor mouse model. Overall, our data support the use of the OMVs in ISV and indicate that ISV efficacy can benefit from the addition of properly selected tumor-specific neo-antigens.

Staphylococcus Aureus Membrane Vesicles Kill Tumor Cells Through a Caspase-1-Dependent Pyroptosis Pathway

“…4 To date, immunotherapy using RNA molecules, immunostimulatory agents, and immune-checkpoint inhibitors has become an increasingly common type of antitumor treatment. [5][6][7] Membrane vesicles (MVs) are spherical, lipid-bilayer, and nanosized (20-400 nm) structures secreted by bacteria during their growth in vitro and in vivo. 8 MVs were first observed in Escherichia coli about 50 years ago, and the MVs of Gram-negative bacteria are mainly released from the outer membrane, namely, outer membrane vesicles (OMVs).…”