In vitro assessment of the effects of vedolizumab binding on peripheral blood lymphocytes

作者：Wyant Timothy^*; Yang Lili; Fedyk Eric

来源：mAbs, 2013, 5(6): 842-850.

DOI：10.4161/mabs.26392

• in vitro
• inflammatory bowel disease
• integrin
• lymphocyte binding
• receptor internalization
• safety profile
• vedolizumab

Vedolizumab (VDZ) is a humanized monoclonal antibody in development for the treatment of inflammatory bowel disease. VDZ binds to the (47) integrin complex and inhibits its binding to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), thus preventing lymphocyte extravasation to gut mucosal tissues. To understand whether VDZ has additional effects that may affect its overall safety as a therapeutic molecule, we examined other potential actions of VDZ. In vitro assays with human peripheral blood lymphocytes demonstrated that VDZ fails to elicit cytotoxicity, lymphocyte activation, and cytokine production from memory T lymphocytes and does not interfere with the suppressive ability of regulatory T cells. Furthermore, we demonstrated that VDZ induces internalization of (47) and that the integrin is rapidly re-expressed and fully functional after VDZ withdrawal. These studies provide insight into the mechanisms underlying the observed safety profile of VDZ in clinical trials.

• 出版日期2013-11-1