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

Abstract

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 αβ integrin which is expressed specifically by a subset of gastrointestinal-homing T lymphocytes. The binding of αβ 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 α 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.

Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis

“…α4β7 integrin is expressed primarily on a subset of CD4 + T cells and mediates homing of these cells specifically to the gut [18, 19]. The counter-receptor of α4β7, mucosal addressin cellular adhesion molecule 1 (MAdCAM-1), is expressed selectively on venule endothelial cells of the gut but not in other organs [18, 20]. Blocking of α4β7 integrin thus results in a gut-specific immunosuppression, while the immunity in extraintestinal tissues remains intact [20].…”

Intractable pyoderma gangrenosum in a Crohn's disease patient on vedolizumab

“…By binding to the α4β7 integrin subunit and blocking its interaction with mucosal addressin cell adhesion molecule-1, vedolizumab inhibits leukocyte adhesion and migration 4, 5. Because IBD is largely driven by lymphocyte trafficking to sites of inflammation, and mucosal addressin cell adhesion molecule-1 is specifically expressed by blood vessels in the gastrointestinal tract, vedolizumab is unique in its gut selectivity and more targeted immunosuppression.…”

Impact of Modern Drug Therapy on Surgery: Crohn's Disease

“…Due to the mode of action as a selective integrin inhibitor in the gut, there is concern that anastomotic healing after bowel resection may be impaired [15]. …”