Figure 1.

Schematic representation for bacteria-based tumor therapy in xenograft mouse tumor models triggered by ultrasound (US)

Engineered designer bacteria harboring synthetic genetic circuits are administered into circulation, after which they can accumulate, colonize, and proliferate inside tumors. The mild temperature increase caused by US stimulation leads to dissociation of the thermosensitive transcriptional repressor TlpA₃₉ from its synthetic promoter P_TlpA. This triggers the localized expression and release of therapeutic agents, such as azurin and PD-L1 nb, from the engineered bacteria. These agents can directly induce apoptosis in tumor cells or stimulate innate and adaptive antitumor immune responses, including activating T cells and NK cells. This comprehensive approach aims to eradicate tumors and prevent tumor relapse.