Engineered Bacterial Membranes as Next-Generation Platforms for Cancer Immunotherapy.

Bacterial membranes, in their natural and engineered forms, including outer membrane vesicles, bacterial ghosts, engineered membrane fragments, and hybrid scaffolds, are emerging as multifunctional immunotherapeutic platforms that merge antigen presentation with intrinsic adjuvanticity. By codisplaying tumor antigens and conserved pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide, flagellin, and CpG motifs, bacterial membranes activate dendritic cells, drive crosspresentation, and elicit durable cytotoxic T-cell memory. Advances in genetic fusion systems (Lpp-OmpA, ClyA, Ag43, and SpyTag/SpyCatcher), lipid A detoxification, and tumor membrane hybridization have transformed bacterial membranes from empirical immunostimulants into programmable vaccine scaffolds. Preclinical studies across melanoma, lung, breast, and glioblastoma models show that these systems reprogram the tumor microenvironment, inducing Th1-polarized immunity, pyroptotic tumor death, and synergy with checkpoint blockade, chemotherapy, and phototherapy. Beyond vesicular formats, membrane fragments and engineered ghosts demonstrate equivalent potential for safe, modular, and scalable vaccine design. Integrating AI-driven antigen discovery, CRISPR-based strain engineering, and automated biofoundries now offers a path toward clinical translation. Collectively, these developments position bacterial membranes as a unifying platform that bridges innate and adaptive immunity for next-generation cancer immunotherapy.