Bacteria-Based Backpacks to Enhance Adoptive Macrophage Transfer against Solid Tumors

Adoptive cell therapy has emerged as a promising approach for cancer treatment. However, the transfer of macrophages exhibits limited efficacy against solid tumors due to the dynamic cellular phenotypic shift from antitumor to protumor states within the immunosuppressive tumor microenvironment. In this study, a strategy of attaching bacteria to macrophages (Mo@bac) is reported that endows adoptively infused macrophages with durable stimulation by leveraging the intrinsic immunogenicity of bacteria. These attached bacteria, referred to as backpacks, are encapsulated with adhesive nanocoatings and can sustainably control the cellular phenotypes in vivo. Moreover, Mo@bac can repolarize endogenous tumor-associated macrophages, leading to a more robust immune response and thus reducing the tumor progression in a murine 4T1 cancer model without any side effects. This study utilizing bacteria as cellular backpacks opens a new avenue for the development of cell therapies. A strategy of attaching bacteria to macrophages (Mo@bac) is reported by means of encapsulating bacterial surface with an adhesive nanocoating. Mo@bac can sustainably stimulate the polarization of macrophages toward antitumor phenotypes in the immunosuppressive tumor microenvironment. In the 4T1 murine models, Mo@bac can remodel the immune microenvironment, induce a robust immune response, and thus enable a potent therapeutic efficacy.image