Anti-Human α4β7 integrin (Vedolizumab) (V204-GRP)

Integrins are a large family of heterodimeric transmembrane molecules that mediate adhesion, migration, cell survival, and cell differentiation. The heterodimeric integrin receptor α4β7 is a cell surface glycoprotein that consists of β7 paired with α4 (CD49d) . The α4β7 integrin is a lymphocyte receptor for the mucosal vascular addressin MADCAM-11. MADCAM-1 is a cell adhesion leukocyte receptor expressed by mucosal venules that helps direct lymphocyte traffic into mucosal tissues and regulates the passage and retention of leukocytes2. α4β7 integrin preferentially mediates migration of lymphocytes into gastrointestinal tissue3. This interaction directs the migration of leukocytes into inflamed intestinal tissue4 and is a target for treating intestinal bowel disease. Vedolizumab is a humanized version of the Act-1 monoclonal antibody that specifically recognizes the α4β7 integrin receptor3,4. Vedolizumab selectively blocks gut lymphocyte trafficking by inhibiting the migration of lymphocytes to the gastrointestinal mucosa during the inflammatory process5. Specifically, migration of memory T lymphocytes into inflamed gastrointestinal parenchymal tissue is inhibited. This is accomplished by blocking immune cell homing to the gut via disruption of α4β7 integrin adhesion on the cell surface of immune cells to its ligand MADCAM-1 on the intestinal endothelium6. Vedolizumab selectively inhibits the adhesion of α 4 β 7 -expressing cells to MADCAM-1 and fibronectin but not VCAM-17. Consequently, vedolizumab does not induce the systemic immunosuppression seen with anti-α4 chain monoclonal antibodies. Rather, vedolizumab yields gut-selective anti-inflammatory activity8. Additionally, vedolizumab does not interfere with trafficking to the central nervous system3.