Anti-adhesion molecule therapies in inflammatory bowel disease: touch and go.
Exploration of the mechanisms underlying the inflammatory bowel diseases [N. Mori, Y. Horie, M.E. Gerritsen, D.C. Anderson, D.N. Granger, Anti-inflammatory drugs and endothelial cell adhesion molecule expression in murine vascular beds. Gut 1999;44:186-95] is a leading field of medical research that drives the application of biological therapies to human diseases. Indeed, many inflammatory mediators can be targeted in the gut by monoclonal antibodies. A recent direction for these therapeutics is targeting of the adhesion molecule family. This molecule family mediates the adhesion and extravasation of leukocytes through the endothelium at sites of inflammation. This is a complex multistep process that has been extensively investigated in recent years; thanks to these studies some adhesion molecules have been identified to specifically mediate leukocyte migration to gut inflammatory sites, like alpha(4)beta(7) integrin. This review outlines the scientific basis behind this therapeutic approach, and describes the principal clinical studies that have been carried out on these new molecules in patients with IBD.
Stefanelli
Tommaso
T
Division of Gastroenterology, Istituto Clinico Humanitas, IRCCS in Gastroenterology, Viale M<anzoni, Rozzano, Milan, Italy.
Malesci
Alberto
A
De La Rue
Sarah A
SA
Danese
Silvio
S
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002448:Cell Adhesion; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology; D039441:Integrin alpha4 / Q000276:immunology* / Q000378:metabolism; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D000069442:Natalizumab; D019087:Selectins / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016023:Integrins; C501380:MLN02 antibody, human; D000069442:Natalizumab; D019087:Selectins; D039441:Integrin alpha4