A self-lysed attenuated Salmonella platform with flagellar displaying mediates tumor therapy

Abstract Conventional cancer therapies such as radiotherapy, chemotherapy, and surgery have obvious limitations in treating solid tumors. Bacteria-mediated tumor therapy has been proven effective in clinical studies and considered to be a promising strategy for tumor treatment. Salmonella, as a facultative anaerobic bacterium, can preferentially colonize tumors and activate the anti-tumor immune response of the host by remodeling the tumor microenvironment. Genetically engineered Salmonella have good tumor targeting ability and controllability, and are highly adaptable to different therapeutic requirements, thus serving as ideal carriers for drug delivery. In this study, RGD4C short peptide was displayed on the constitutively expressed flagellum of attenuated Salmonella Typhimurium to develop a vector suitable for fast moving and targeting and deep colonizing within hypoxic region in tumor. At the same time, in order to safely and effectively exert the anti-tumor activity in Salmonella, a regulated lysis system based on the new lysing protein M4lys encoded by phage was applied to lyse Salmonella peptidoglycan to release endogenous and exogenous anti-tumor molecules, and balanced lethal vector-host system was used to deliver exogenous anti-tumor molecules. In all, a novel genetically engineered live Salmonella was successfuly constructed and able to deliver exogenous anti-tumor molecules to exert the anti-tumor activity for tumor therapy.