Biomaterials Based on Bacteria for Cancer Clinical Therapy.

Abstract

Cancer remains a major global health burden, necessitating innovative therapies. Bacterial therapy has reemerged as a transformative strategy, particularly for the potential to overcome resistance to conventional treatments. Bacteria could selectively colonize the hypoxic, acidic, and immunosuppressive tumor microenvironment. Besides, synthetic biology has enabled these bacteria to be engineered into precise living therapeutics, capable of localized drug delivery, targeted immune modulation, and remodeling of the tumor microenvironment. This review systematically explores the mechanisms by which engineered bacteria exert antitumor effects, including direct oncolysis, immunogenic cell death, and reversal of immunosuppression. Furthermore, the synergistic potential of bacterial therapy with standard therapies is discussed. Bacteria can sensitize tumors to chemotherapy through prodrug activation or reverse microbiota-mediated chemoresistance. In radiotherapy, bacteria could act as radiosensitizers and radioprotectors while amplifying abscopal effects. Combined with immunotherapy, they effectively convert immunologically "cold" tumors into "hot" ones, enhancing the application of immune checkpoint inhibitors. The role of the gut microbiota in shaping systemic antitumor immunity is also discussed. Finally, the article critically assesses the clinical translation landscape, examining representative strains in development, addressing safety and manufacturing challenges, and highlighting future directions. This review aims to provide a foundational perspective for developing safer and more effective bacterially mediated anticancer strategies.