Rapid resolution of chronic colitis in the cotton-top tamarin with an antibody to a gut-homing integrin alpha 4 beta 7

Hesterberg, PE; Winsor-Hines, Dawn; Briskin, MJ; Soler-Ferran, Dulce; Merrill, C; Mackay, Charles R.; Newman, Walter; Ringler, DJ

doi:10.1053/gast.1996.v111.pm8898653

Cited by 312 publications

(185 citation statements)

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“…[10][11][12] Preclinical studies have shown that monoclonal antibodies against a 4 integrin reduce inflammation and symptoms of disease in tamarins with inflammatory bowel disease. 13,14 Natalizumab (Antegren, Elan Pharmaceuticals and Biogen), a recombinant, humanized monoclonal antibody against a 4 integrin, improved the signs and symptoms of patients with Crohn's disease or ulcerative colitis in two pilot studies. 15,16 We conducted a large, randomized, placebo-controlled trial of this selective adhesion-molecule inhibitor in patients with moderate-to-severe Crohn's disease.…”

mentioning

confidence: 99%

Natalizumab for Active Crohn's Disease

et al. 2003

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confidence: 99%

Natalizumab for Active Crohn's Disease

et al. 2003

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“…Animal models of colitis have shown that antibodies to a4-integrin, a4b7-integrin or its ligand MAdCAM-1 reduce T cell mediated intestinal inflammation and abrogate symptoms of colitis [18][19][20][21]. The promising results of these pre-clinical studies led to human trials using humanized anti a4-integrin or anti-a4b7-integrin antibodies.…”

Section: Anti A4-integrin Therapy Of Inflammatory Bowel Diseasementioning

confidence: 99%

“…Neutrophils express only low levels of a4 integrins and rather rely on b2 integrins to travel to sites of inflammation [26]. Thus, the beneficial effect of anti-a4-integrin therapy in Crohn's disease may either depend on the inhibition of the recruitment of T cell populations providing secondary signals in the gut, such as cytokines and chemokines that are needed to sustain neutrophil recruitment [18] or on entirely different functions of a4-integrins.…”

Section: Anti A4-integrin Therapy Of Inflammatory Bowel Diseasementioning

confidence: 99%

Therapeutic targeting of α4-integrins in chronic inflammatory diseases: tipping the scales of risk towards benefit?

Engelhardt

Briskin

2005

Eur. J. Immunol.

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Inhibition of leukocyte trafficking via a4-integrin antibody blockade has recently become a validated therapeutic approach for several inflammatory diseases, including multiple sclerosis, ulcerative colitis and Crohn's disease. In the midst of this recent success, 3 patients receiving chronic treatment with the anti-a4 antagonist natalizumab (Tysabri) for the treatment of multiple sclerosis or Crohn's disease, developed JC-virus related progressive multifocal leukoencephalopathy (PML). These unforeseen consequences suggest that long term blockade of a4-integrins might prevent trafficking of non-pathogenic lymphocytes that are essential for viral immunosurveillance. In the current issue of the European Journal of Immunology Bjursten and colleagues report that long term treatment with anti-a4-integrin antibodies results in exacerbation of the murine model of colitis induced by the targeted deletion of the heterotrimeric G protein subunit Gai2. In order to properly evaluate the efficacy and safety of anti-a4-integrin therapy, the relationship between these observations in an immunologically altered animal model and human clinical disease needs to be carefully measured.

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“…1 The importance of α4 integrin signaling in various chronic inflammatory diseases 2 and tumor metastases 3 has led to the development of several α4 antagonists. 4 These include antibodies that bind α4 integrins, 5,6 peptidomimetics that block integrin binding, [7][8][9] and small molecules that disrupt the α4 integrin-paxillin complex. 10 Inhibition of α4 integrin signaling by targeting proteins downstream of α4 integrin may offer an alternative approach for modulating α4 integrinmediated leukocyte trafficking, as well as provide new insights into integrin dependent signaling pathways.…”

Section: Introductionmentioning

confidence: 99%