Surface display of co-stimulatory ligand B7H2 on engineered bacteria enhances tumor immunotherapy
TL;DR
The surface-engineered bacteria are reported as the living therapeutic for tumor immunotherapy with outstanding potential for tumor immunotherapy when combined with functional materials or rewired with rationally designed gene circuits.
Abstract
Summary 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.