Abstract:
BACKGROUND:Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which is currently treated with injected monoclonal antibodies specific for tumor necrosis factor (TNF). We developed and characterized AVX-470, a novel polyclonal antibody specific for human TNF. We evaluated the oral activity of AVX-470m, a surrogate antibody specific for murine TNF, in several well-accepted mouse models of IBD. METHODS:AVX-470 and AVX-470m were isolated from the colostrum of dairy cows that had been immunized with TNF. The potency, specificity, and affinity of both AVX-470 and AVX-470m were evaluated in vitro and compared with infliximab. AVX-470m was orally administered to mice either before or after induction of colitis, and activity was measured by endoscopy, histopathology, immunohistochemistry, and quantitative measurement of messenger RNA levels. Colitis was induced using either 2,4,6-trinitrobenzene sulfonate or dextran sodium sulfate. RESULTS:AVX-470 and AVX-470m were shown to be functionally comparable in vitro. Moreover, the specificity, neutralizing potency, and affinity of AVX-470 were comparable with infliximab. Orally administered AVX-470m effectively reduced disease severity in several mouse models of IBD. Activity was comparable with that of oral prednisolone or parenteral etanercept. The antibody penetrated the colonic mucosa and inhibited TNF-driven mucosal inflammation with minimal systemic exposure. CONCLUSIONS:AVX-470 is a novel polyclonal anti-TNF antibody with an in vitro activity profile comparable to that of infliximab. Oral administration of a surrogate antibody specific for mouse TNF is effective in treating mouse models of IBD, delivering the anti-TNF to the site of inflammation with minimal systemic exposure.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Bhol KC,Tracey DE,Lemos BR,Lyng GD,Erlich EC,Keane DM,Quesenberry MS,Holdorf AD,Schlehuber LD,Clark SA,Fox BSdoi
10.1097/MIB.0b013e3182a11958subject
Has Abstractpub_date
2013-10-01 00:00:00pages
2273-81issue
11eissn
1078-0998issn
1536-4844journal_volume
19pub_type
杂志文章abstract:BACKGROUND:Multi-matrix (MMx), a new delivery system for mesalazine, seems to release 5-aminosalicyclic acid (5-ASA) preferentially in the sigmoid colon. This study had 2 objectives: (1) to evaluate the therapeutic response to MMx in patients with active left-sided disease and (2) to gain additional insights as to how ...
journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1097/01.mib.0000158386.25660.1e
更新日期:2005-05-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izy032
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000939
更新日期:2016-11-01 00:00:00
abstract::Skin manifestations are common in patients suffering from inflammatory bowel disease (IBD) and can be associated with the disease itself, with nutritional deficiencies, or with therapy. All drugs currently used for treating IBD have the potential to cause dermatologic manifestations that can have a wide range of clini...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0b013e3182802c07
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pub_type: 杂志文章
doi:10.1097/MIB.0000000000000524
更新日期:2015-11-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/MIB.0000000000000036
更新日期:2014-06-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000894
更新日期:2016-10-01 00:00:00
abstract::Treatment adherence is of critical importance in the management of patients with IBD. Poor adherence can lead to increased disease activity, loss of response to therapy, and increased costs of care. It has been well established that adherence to long-term therapy for chronic illnesses is extremely poor, averaging arou...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0000000000000581
更新日期:2015-12-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000825
更新日期:2016-07-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章
doi:10.1002/ibd.20895
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND:Chronic inflammation in ulcerative colitis (UC) is a sizeable risk factor for colorectal cancer (CRC). Interleukin-13 (IL-13) is elevated in the UC mucosa and may induce dysregulated signaling in neighboring intestinal epithelial cells (IECs) and thus function as a tumorogenic cytokine. METHODS:Expression o...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,收录出版
doi:10.1002/ibd.21133
更新日期:2010-05-01 00:00:00
abstract:BACKGROUND:P-glycoprotein (P-gp), the product of the multidrug resistance gene (MDR), is an ATP-dependent transmembrane pump, which is expressed in multiple cell lineages including epithelial and hematopoetic cells. The human MDR gene is located on chromosome 7 (7q21.1), a susceptibility loci for inflammatory bowel dis...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20824
更新日期:2009-05-01 00:00:00
abstract:Background:Tumor necrosis factor alpha (TNF-α) inhibitors are linked with increased risk of reactivation of active tuberculosis. The QuantiFERON-TB Gold In-Tube test is approved for screening latent tuberculosis infection in children and adults. There are limited data on the test performance in children on long-term tr...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izx077
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abstract:BACKGROUND:It is unclear if traditional histopathology and noninvasive blood-based tests are sufficiently accurate to detect cytomegalovirus (CMV) reactivation in inflammatory bowel disease. Therefore, we assessed the diagnostic accuracy of these tests compared with immunohistochemistry (IHC) and tissue polymerase chai...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析,评审
doi:10.1097/MIB.0000000000001073
更新日期:2017-04-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00054725-200207000-00005
更新日期:2002-07-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析
doi:10.1097/MIB.0000000000000771
更新日期:2016-06-01 00:00:00
abstract:BACKGROUND:Infliximab is efficacious in the management of moderate to severe Crohn's disease (CD). There are limited data regarding performance of infliximab in patients who require reinitiation of maintenance dosing following previous irregular exposure. METHODS:This was a retrospective, observational study of CD pat...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21164
更新日期:2010-07-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1002/ibd.20933
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20139
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izz282
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pub_type: 杂志文章,评审
doi:10.1002/ibd.21247
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journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章
doi:10.1097/MIB.0b013e318280fcb9
更新日期:2013-02-01 00:00:00
abstract:BACKGROUND:Optimal levels of adalimumab (ADA) have not been defined according to the ultimate goal of inflammatory bowel disease treatment--histologic and/or endoscopic healing. The aim of this study was to assess the relationship between random serum ADA levels and histologic and endoscopic healing in patients with in...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000689
更新日期:2016-02-01 00:00:00
abstract::MicroRNAs (miRNAs) are single-stranded RNA molecules, which influence the translation of messenger RNA and hence protein synthesis. The altered expression of miRNAs in disease states in cancer and autoimmune diseases including inflammatory bowel disease is providing new insights into disease pathogenesis. This underst...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
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更新日期:2015-05-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.mib.0000165115.18310.e7
更新日期:2005-07-01 00:00:00
abstract::Clinical and epidemiological studies have revealed that the incidence of colorectal cancer associated with ulcerative colitis increases with long-term chronic inflammation. Careful endoscopic observation and histological studies to check for dysplasia in the colon are important in detecting neoplasia. Current surveill...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.20267
更新日期:2008-02-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/00054725-200203000-00008
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21298
更新日期:2010-12-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0000000000000477
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
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