Engineered bacterial outer membrane vesicles: a versatile bacteria-based weapon against gastrointestinal tumors

Abstract

Outer membrane vesicles (OMVs) are nanoscale lipid bilayer structures released by gram-negative bacteria. They share membrane composition and properties with their originating cells, making them adept at traversing cellular barriers. These OMVs have demonstrated exceptional membrane stability, immunogenicity, safety, penetration, and tumor-targeting properties, which have been leveraged in developing vaccines and drug delivery systems. Recent research efforts have focused on engineering OMVs to increase production yield, reduce cytotoxicity, and improve the safety and efficacy of treatment. Notably, gastrointestinal (GI) tumors have proven resistant to several traditional oncological treatment strategies, including chemotherapy, radiotherapy, and targeted therapy. Although immune checkpoint inhibitors have demonstrated efficacy in some patients, their usage as monotherapy remains limited by tumor heterogeneity and individual variability. The immunogenic and modifiable nature of OMVs makes them an ideal design platform for the individualized treatment of GI tumors. OMV-based therapy enables combination therapy and optimization of anti-tumor effects. This review comprehensively summarizes recent advances in OMV engineering for GI tumor therapy and discusses the challenges in the clinical translation of emerging OMV-based anti-tumor therapies.

Harnessing Bacterial Extracellular Vesicle Immune Effects for Cancer Therapy

“…As described in the section below, a different approach could involve engineering to alter the intrinsic properties of bEVs. This area of research is far more advanced in the field of mammalian EVs and synthetic nanoparticles [ 123 – 126 ], which could provide significant insight for bEV applications as well. For example, mammalian EV circulating time was significantly increased when they were engineered to express the “don't-eat-me” signal, CD47, which inhibits phagocytosis by macrophages upon ligation with its receptor, SIRPα [ 127 ].…”

Arginine-linked HPV-associated E7 displaying bacteria-derived outer membrane vesicles as a potent antigen-specific cancer vaccine

“…In recent years, studies have shown that gram-negative bacteria can naturally release outer membrane vesicles (OMVs), which comprises of lipopolysaccharides (LPS), outer membrane proteins, periplasmic proteins, and phospholipids and can serve as carriers for various substances such as toxins, metabolites, enzymes, virulence factors, and genetic material (DNA and RNA) [ 11 – 13 ]. Unlike attenuated bacteria, OMVs are considered safer and can effectively stimulate the immune system by delivering key immunogens from their parent bacteria [ 13 – 15 ]. Genetic engineering techniques have shown that the construction of recombinant OMVs improves target precision through surface protein and carries exogenous proteins for improved immunogenicity [ 16 , 17 ].…”