Patients afflicted with ulcerative colitis (UC) are at increased risk of colorectal cancer. While its causes are not fully understood, UC is associated with defects in colonic epithelial barriers that sustain inflammation of the colon mucosa caused by recruitment of lymphocytes and neutrophils into the lamina propria. Based on genetic evidence that attenuation of the bridging integrator 1 (Bin1) gene can limit UC pathogenicity in animals, we have explored Bin1 targeting as a therapeutic option. Early feasibility studies in the dextran sodium sulfate mouse model of experimental colitis showed that administration of a cell-penetrating Bin1 monoclonal antibody (Bin1 mAb 99D) could prevent lesion formation in the colon mucosa in part by preventing rupture of lymphoid follicles. In vivo administration of Bin1 mAb altered tight junction protein expression and cecal barrier function. Strikingly, electrophysiology studies in organ cultures showed that Bin1 mAb could elevate resistance and lower
Thomas, Sunil; Hoxha, Kevther; Alexander, Walker; Gilligan, John; Dilbarova, Rima; Whittaker, Kelly; Kossenkov, Andrew; Prendergast, George C.; and Mullin, James M., "Intestinal barrier tightening by a cell-penetrating antibody to Bin1, a candidate target for immunotherapy of ulcerative colitis." (2018). Kimmel Cancer Center Papers, Presentations, and Grand Rounds. Paper 64.
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