Surface Modification of Bacteria to Optimize Immunomodulation for Advanced Immunotherapy

Abstract Bacteria have been widely exploited as therapeutic agents for immunotherapy due to their native immunogenicity, living characteristic, and genetic manipulability. However, conventional bacteria‐based immunotherapy often suffers from dose‐dependent safety issues and poor treatment efficacy. Harnessing surface modification of bacteria to carry additional immune modulators has emerged as a promising strategy to reduce bacterial dose and synergistically enhance the activation of immune responses. In this paper, bacteria‐mediated immunomodulation and the underlying mechanisms are introduced, followed by a summarization on the concept of using surface‐modification approaches including physical encapsulation, chemical conjugation, and metabolic labelling to combine diverse immune functions. The applications of modified bacteria as therapeutics for immunotherapy toward cancer and inflammatory bowel disease have been expounded further. Both challenges and future perspectives regarding the utilization of surface‐modified bacteria for immunomodulation are also proposed. This work offers unique insights into developing safe yet potent bacteria‐based therapeutics for advanced immunotherapy.