Novel approaches to treating inflammatory bowel disease: targeting alpha-4 integrin.
Crohn's disease involves persistent recruitment of leukocytes into gut tissue, coupled with dysregulated activation of specific immune cell function. Adhesion molecules expressed by circulating leukocytes, such as alpha 4 integrin, mediate their attachment to vascular endothelial cells lining blood vessels within the intestine and facilitate their migration into the tissue. Through interactions with extracellular matrix molecules, adhesion molecules then support immune cell activation and survival within the intestinal wall. Agents that interfere with these adhesive interactions hold great potential for suppressing the cycle of leukocyte infiltration and activation, and thereby, for ameliorating chronic inflammation. This article will discuss clinical data for a humanized monoclonal antibody against alpha 4 integrin, natalizumab, which is the first alpha 4 integrin antagonist in a new class of biotechnology agents referred to as selective adhesion molecule inhibitors.
Sandborn
William J
WJ
Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Yednock
Ted A
TA
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D017322:Clinical Trials, Phase II as Topic; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000473:pathology; D003424:Crohn Disease / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000473:pathology; D039441:Integrin alpha4 / Q000187:drug effects*; D008297:Male; D000069442:Natalizumab; D016032:Randomized Controlled Trials as Topic; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab; D039441:Integrin alpha4