Surface display of co-stimulatory ligand B7H2 on engineered bacteria enhances tumor immunotherapy.

Abstract

Bacteria-based living therapeutics exhibit outstanding potential for tumor immunotherapy when combined with functional materials or rewired with rationally designed gene circuits. To stimulate T cells precisely and effectively, herein, we report the surface-engineered bacteria as the living therapeutic for tumor immunotherapy. Escherichia coli cells are genetically programmed to display surface-anchored B7H2 to provide immunological co-stimulation signal of T cells and Histag to coordinate with ZnS quantum dots. In tumors, B7H2 induces the co-stimulatory ICOS-B7H2 signal at the molecular level and triggers the stimulation of cytotoxic T cells, the polarization of helper T cells, the release of cytokines, and long term antitumor immunological memory. Meanwhile, the coordinated ZnS quantum dots image tumors and synergize with B7H2 to enhance immune effects by activating the cGAS/STING pathway. With functional domains displaying on the bacterial surface, we establish an efficient living therapeutic approach for tumor immunotherapy.