Human MAdCAM-1 antibodies as targeted immune modulators

Inflammatory bowel disease (IBD) is a highly prevalent condition characterized by chronic inflammation present along the gastrointestinal (GI) tract. Mitigation of symptoms is critical to the quality of life of patients. Targeting Mucosal Addressin-Cell Adhesion Molecule 1 (MAdCAM-1), a cell surface antigen predominantly expressed on endothelial cells of venules located in the lamina propria of the small intestine and colon, represents an attractive marker to locally deliver therapeutics that dampen inflammation associated with IBD. As such, mAbs derived from eight hybridoma clones were characterized, shown to bind to human MAdCAM-1 with dissociation constants in the low to sub-nanomolar range and were able to detect human MAdCAM-1 transiently expressed on the surface of cells. Interestingly, only 4 of these antibodies detected MAdCAM-1 on the venules of human small intestinal tissue by immunohistochemistry. Importantly, these 4 antibody clones, 1B10, 11C3, 7A2, and 2F3 behave as strong antagonists, able to block MAdCAM-1 costimulation of primary human CD4⁺ T cells. These antibodies or related anti hMaDCAM-1 scFv bispecifics may serve as targeted therapeutics to the GI tract for treating IBD.