Rational and clinical development of the anti-MAdCAM monoclonal antibody for the treatment of IBD

Expert Opin Biol Ther. 2019 Apr;19(4):361-366. doi: 10.1080/14712598.2019.1576631. Epub 2019 Feb 11.

Abstract

Introduction: Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression in gut-associated lymphoid tissue is upregulated in patients with inflammatory bowel disease (IBD). Blocking adhesion molecules and thereby inhibiting migration of lymphocytes into sites of inflammation in the gut is an attractive new treatment target in drug development for IBD.

Areas covered: This review discusses the preclinical and clinical experience on SHP647 (previously called PF-00547659 and PF-00547,659), a fully human IgG2K monoclonal antibody that binds to MAdCAM-1 to selectively reduce lymphocyte homing to the intestinal tract.

Expert opinion: Blocking endothelial adhesion molecule MAdCAM-1 could represent an attractive target for the treatment of IBD. In the next years, the results from the phase III studies as well as data to support therapeutic drug monitoring based on drug levels to guide and optimize individual therapy will become available. Furthermore, much effort is put in the development of clinical prediction models to predict which drug is optimal for an individual patient.

Keywords: Crohn’s disease; anti-MadCAM; inflammatory bowel disease; integrins; therapy; ulcerative colitis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Cell Adhesion Molecules / immunology*
  • Clinical Trials as Topic
  • Colitis, Ulcerative / drug therapy
  • Colitis, Ulcerative / pathology
  • Crohn Disease / drug therapy
  • Crohn Disease / pathology
  • Drug Evaluation, Preclinical
  • Humans
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / pathology
  • Mucoproteins / immunology*

Substances

  • Antibodies, Monoclonal, Humanized
  • Cell Adhesion Molecules
  • MADCAM1 protein, human
  • Mucoproteins
  • ontamalimab