Reprogramming tumor-colonizing bacteria into modular immune cell engagers

Immune engagers redirect lymphocytes against cancer, but poor tumor access, immunosuppression and systemic toxicity constrain efficacy. We developed live immune modulating engagers (LIME): non-pathogenic, tumor-tropic Escherichia coli displaying tandem single chain variable fragments targeting a tumor antigen and an activating T or NK receptor.

LIME bridged effector and tumor cells, reprogrammed effector transcription, and enhanced cytotoxicity across cancer cell lines and patient-derived organoids. In mice, LIME selectively accumulated in tumors, outperformed tarlatamab in small cell lung cancer, and induced durable lymphoma immunity. In pancreatic cancer, a RAS(ON) inhibitor enhanced LIME-driven T cell infiltration and tumor reactive antibodies, revealing an adaptive myeloid PD-L1 program overcome by PD-L1 blockade.