Gut-Selective Integrin-Targeted Therapies for Inflammatory Bowel Disease

Journal of Crohn's & Colitis
Christopher A LambEugene C Butcher

Abstract

Integrins are cell surface receptors with bidirectional signalling capabilities that can bind to adhesion molecules in order to mediate homing of leukocytes to peripheral tissues. Gut-selective leukocyte homing is facilitated by interactions between α4β7 and its ligand, mucosal addressin cellular adhesion molecule-1 [MAdCAM-1], while retention of lymphocytes in mucosal tissues is mediated by αEβ7 binding to its ligand E-cadherin. Therapies targeting gut-selective trafficking have shown efficacy in inflammatory bowel disease [IBD], confirming the importance of leukocyte trafficking in disease pathobiology. This review will provide an overview of integrin structure, function and signalling, and highlight the role that these molecules play in leukocyte homing and retention. Anti-integrin therapeutics, including gut-selective antibodies against the β7 integrin subunit [etrolizumab] and the α4β7 integrin heterodimer [vedolizumab and abrilumab], and the non-gut selective anti-α4 integrin [natalizumab], will be discussed, as well as novel targeting approaches using small molecules.

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Citations

Jan 18, 2020·Expert Opinion on Biological Therapy·Ferdinando D'AmicoLaurent Peyrin-Biroulet
Jul 14, 2019·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Pavine L C LefevreNiels Vande Casteele
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Nov 24, 2020·Gastroenterology Research and Practice·Shun MurasugiKatsutoshi Tokushige
Nov 8, 2020·Journal of Pharmaceutical Sciences·Shno AsadAlexandra Teleki
Aug 28, 2021·International Journal of Molecular Sciences·Claudia GüntherBeate Winner
Sep 2, 2021·Clinical and Experimental Gastroenterology·John GubatanSidhartha Sinha
Oct 7, 2021·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Nicola J WyattChristopher A Lamb
Sep 26, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mary E KeirChristopher A Lamb
Jun 24, 2021·Journal of Gastroenterology and Hepatology·Sandro ArdizzoneGiovanni Maconi

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