Vedolizumab for the Treatment of IBD: A Selective Therapeutic Approach Targeting Pathogenic a4b7 Cells

被引:49
作者
Jovani, Manol [1 ]
Danese, Silvio [1 ]
机构
[1] Ist Clin Humanitas, Dept Gastroenterol, IBD Ctr, Milan, Italy
关键词
Inflammatory bowel disease; Crohn's disease; ulcerative colitis; alpha(4)beta(7) integrin; anti-integrins; adhesion molecules; natalizumab; vedolizumab; etrolizumab; MAdCAM-1; CAM; ACTIVE CROHNS-DISEASE; INFLAMMATORY BOWEL DISEASES; ULCERATIVE-COLITIS; MAINTENANCE THERAPY; T-CELLS; INTEGRIN ALPHA-4-BETA-7; ADHESION MOLECULE-1; HUMANIZED ANTIBODY; NATALIZUMAB; MADCAM-1;
D O I
10.2174/13894501113146660206
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Inflammatory bowel diseases (IBD) are characterized by a persistent recruitment of large quantities of leucocytes from the blood to the gut mucosa. Adhesion molecules, such as integrins and their ligands, are the main players in this complex process. Leucocyte traffic control using a specific integrin inhibitors, such as natalizumab, has been plagued by severe systemic effects. The alpha(4)beta(7) - integrin and its ligand, the MadCAM-1, have been of special interest, since they are found exclusively on the gut-homing lymphocyte subpopulations and in the intestinal mucosa respectively. It follows that inhibition of such molecules should offer gut-specific immunosuppression, without the systemic effects of aspecific integrin-antagonists. We review the role of vedolizumab, a humanized antibody against the alpha(4)beta(7) - integrin, in both ulcerative colitis (UC) and Crohn's disease (CD). Results from clinical trials show that vedolizumab is effective in the induction and maintenance of remission in active CD and UC and has a very good safety profile. These data allow to confidently prospect that vedolizumab will be an important therapeutic option in the future of IBD treatment.
引用
收藏
页码:1433 / 1443
页数:11
相关论文
共 41 条
[1]   Tissue-tropic effector T cells: generation and targeting opportunities [J].
Agace, William W. .
NATURE REVIEWS IMMUNOLOGY, 2006, 6 (09) :682-692
[2]   Differential expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in ulcerative colitis and Crohn's disease [J].
Arihiro, S ;
Ohtani, H ;
Suzuki, M ;
Murata, M ;
Ejima, C ;
Oki, M ;
Kinouchi, Y ;
Fukushima, K ;
Sasaki, I ;
Nakamura, S ;
Matsumoto, T ;
Torii, A ;
Toda, G ;
Nagura, H .
PATHOLOGY INTERNATIONAL, 2002, 52 (5-6) :367-374
[3]   Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease [J].
Baert, F ;
Noman, M ;
Vermeire, S ;
Van Assche, G ;
D'Haens, G ;
Carbonez, A ;
Rutgeerts, P .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (07) :601-608
[4]   Gastroenterology 1 - Inflammatory bowel disease: cause and immunobiology [J].
Baumgart, Daniel C. ;
Carding, Simon R. .
LANCET, 2007, 369 (9573) :1627-1640
[5]   ALPHA-4-BETA-7-INTEGRIN MEDIATES LYMPHOCYTE BINDING TO THE MUCOSAL VASCULAR ADDRESSIN MADCAM-1 [J].
BERLIN, C ;
BERG, EL ;
BRISKIN, MJ ;
ANDREW, DP ;
KILSHAW, PJ ;
HOLZMANN, B ;
WEISSMAN, IL ;
HAMANN, A ;
BUTCHER, EC .
CELL, 1993, 74 (01) :185-195
[6]   Increased numbers of circulating hematopoietic stem/progenitor cells are chronically maintained in patients treated with the CD49d blocking antibody natalizumab [J].
Bonig, Halvard ;
Wundes, Annette ;
Chang, Kai-Hsin ;
Lucas, Sylvia ;
Papayannopoulou, Thalia .
BLOOD, 2008, 111 (07) :3439-3441
[7]  
Briskin M, 1997, AM J PATHOL, V151, P97
[8]   Lymphocyte homing and homeostasis [J].
Butcher, EC ;
Picker, LJ .
SCIENCE, 1996, 272 (5258) :60-66
[9]  
Cesarini M, 2013, EXPERT REV CLIN IMMU, V9, P301, DOI [10.1586/ECI.13.11, 10.1586/eci.13.11]
[10]  
Danese S, 2006, WORLD J GASTROENTERO, V12, P4807