P0017Intestine-Targeted Delivery of Hepatocyte Growth Factor Using AccumBody® Ameliorates Colitis in a Dextran Sulfate Sodium-Induced Mouse Model

Background Inflammatory bowel diseases (IBD) are chronic, relapsing disorders characterized by persistent mucosal inflammation and impaired epithelial repair. While current biologic therapies primarily suppress inflammation, they do not directly promote mucosal healing. Hepatocyte growth factor (HGF) is known to enhance epithelial regeneration, but its therapeutic potential is limited by rapid systemic clearance and hepatic sequestration. AccumBody® is an antibody-based platform designed to deliver drugs specifically to the intestine; however, its efficacy in intestinal inflammation remains to be elucidated. In this study, we investigated whether intestine-targeted delivery of HGF conjugated with AccumBody® (HGF-AB) could improve therapeutic outcomes in a murine model of colitis. Methods Acute colitis was induced in C57BL/6J mice by administration of dextran sulfate sodium (DSS). Mice were treated via intraperitoneal injection with phosphate-buffered saline (PBS), free HGF, or HGF-AB. Each group included 5 mice. Clinical parameters, including body weight and disease activity index (DAI), were monitored throughout the experiment. On day 8, colon length, histopathology, and serum HGF concentrations were assessed. Histological damage was evaluated using the Mouse Colitis Histology Index (MCHI). Statistical analyses were performed using the Kruskal–Wallis test followed by Dunn’s multiple comparisons, as appropriate. A p-value < 0.05 was considered statistically significant. Results Mice treated with HGF-AB exhibited significantly attenuated weight loss, lower DAI scores, and reduced colon shortening compared to those receiving PBS or free HGF. Histological analysis revealed markedly reduced tissue injury in the HGF-AB group, with lower MCHI scores indicating preserved crypt architecture, retention of goblet cells, and diminished submucosal inflammation. Serum HGF levels were significantly higher in the HGF-AB group than in the free HGF and control groups, reflecting the pharmacokinetic advantages conferred by the antibody-based delivery system. Conclusion Targeted intestinal delivery of HGF via AccumBody® significantly improved both clinical and histological outcomes in DSS-induced colitis. The therapeutic benefits of HGF-AB may be attributed to enhanced epithelial regeneration and modulation of local inflammatory responses through sustained HGF signaling in colonic tissue. Further studies are warranted to evaluate the long-term safety and efficacy of HGF-AB and to explore its potential in chronic colitis models and clinical translation. Conflict of interest: Dr. Maeda, Nobuhisa: No conflict of interest Kanmura, Shuji: Morinaga, Yuko: No conflict of interest Mori, Satoshi: No conflict of interest Tanaka, Akihito: No conflict of interest Maeda, Hidehito: No conflict of interest Sasaki, Fumisato: No conflict of interest