An Overview of the Mechanism of Action of the Monoclonal Antibody Vedolizumab

Vedolizumab is a novel therapeutic monoclonal antibody recently approved for the treatment of moderately to severely active ulcerative colitis and Crohn's disease in adults who have failed at least one conventional therapy. An integrin antagonist, vedolizumab binds to the alpha(4)beta(7) integrin which is expressed specifically by a subset of gastrointestinal-homing T lymphocytes. The binding of alpha(4)beta(7) integrin to mucosal addressin cell adhesion molecule-1 expressed on the surface of mucosal endothelial cells is a crucial component of the gut-selective homing mechanism for lymphocytes. In contrast, other monoclonal antibodies approved for the treatment of inflammatory bowel diseases, such as tumour necrosis factor a antagonists and the integrin antagonist natalizumab, act systemically or on multiple targets to reduce inflammation. The unique gut selectivity of vedolizumab may contribute to the favourable benefit-risk profile observed in vedolizumab clinical trials. In this review, we summarise data from the preclinical development of vedolizumab and describe the current understanding of the mechanism of action as it relates to other biological therapies for inflammatory bowel disease.