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EcN-ePD-L1-mFc is an engineered live biotherapeutic product (LBP) designed for the localized treatment of inflammatory bowel disease (IBD). It utilizes the probiotic *Escherichia coli* Nissle 1917 (EcN) as a chassis, which has been modified by removing endogenous plasmids (pMUT1 and pMUT2) to reduce metabolic burden and antibiotic resistance. The bacterium is engineered to express a fusion protein consisting of the extracellular domain of murine Programmed Death-Ligand 1 (mPD-L1) and a mouse Fc fragment (mFc), anchored to the bacterial surface and outer membrane vesicles (OMVs) via a cytolysin A (ClyA) fragment. Expression is conditionally controlled by an L-arabinose-inducible araBAD promoter to ensure gut-targeted delivery and minimize systemic exposure. The therapeutic mechanism involves the delivery of PD-L1 to the intestinal mucosa, where it acts as an agonist for the PD-1 receptor on T cells, thereby inhibiting effector T cell proliferation, promoting regulatory T cell (Treg) expansion, and restoring intestinal barrier integrity and microbiota balance.
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