Engineered Bacteria Factory Integrating Drug Delivery and Antibody Manufacture for Activating the STING Signal Pathway Mediated Tumor Immunotherapy

Macrophages show great potential for application in cellular immunotherapy, but are limited by immune checkpoints (ICBs). Immune checkpoint inhibitors (ICIs) can effectively block immune escape pathways and alleviate immune suppression in the tumor microenvironment (TME). Here, we constructed hypoxia response bacteria (HRB) that specifically expressed CD47 antibody (aCD47) under hypoxic conditions in the TME, enabling the in situ synthesis of ICIs at the tumor site. In addition, this study further prepared responsive liposomes for encapsulating the STING agonist cGAMP and modified them by covalent attachment to the HRB surface to form the composite material HRB@LC. This composite system can synergistically block CD47‐SIRPα‐mediated immune escape and activate the STING signal pathway, thereby enhancing systemic antitumor immune responses and significantly improving the efficacy of immunotherapy.