A novel organ-targeted antibody conjugated to hepatocyte growth factor ameliorates colitis in a mouse model

Inflammatory bowel disease (IBD) is a chronic disease characterized by persistent mucosal inflammation and impaired epithelial repair. Hepatocyte growth factor (HGF) is a potent epithelial regeneration factor; however, its rapid clearance after systemic administration and organ non-specificity limit its clinical application. In this study, we aimed to investigate the effects of a gut-directed antibody conjugated to HGF on colitis. Mouse models of dextran sulfate sodium (DSS)-induced acute experimental colitis were intraperitoneally administered phosphate-buffered saline (PBS), free recombinant HGF, or an HGF- glycoprotein A33-specific targeting antibody complex (HGF-AB), and their body weight, disease activity index (DAI), colon length, mouse colitis histology index (MCHI), and serum HGF concentration were measured. HGF-AB treatment significantly suppressed body weight loss, reduced DAI, and maintained colon length than PBS or HGF monotherapy. The epithelial structure and inflammatory damage were significantly protected in the HGF-AB-treated group. Serum HGF concentrations were higher in the HGF-AB-treated group than in the free HGF-treated group, suggesting improved pharmacokinetic stability via antibody conjugation. HGF-AB regulated mucosal immune responses by suppressing proinflammatory cytokine transcripts and enhancing anti-inflammatory IL-10 expression. Overall, the findings established organ-targeted regenerative therapy as a promising adjunctive strategy to complement the existing anti-inflammatory treatments and promote healing in IBD.