dc.contributor.author | Crowe, JS | en_US |
dc.contributor.author | Roberts, KJ | en_US |
dc.contributor.author | Carlton, TM | en_US |
dc.contributor.author | Maggiore, L | en_US |
dc.contributor.author | Cubitt, MF | en_US |
dc.contributor.author | Clare, S | en_US |
dc.contributor.author | Harcourt, K | en_US |
dc.contributor.author | Reckless, J | en_US |
dc.contributor.author | MacDonald, TT | en_US |
dc.contributor.author | Ray, KP | en_US |
dc.contributor.author | Vossenkämper, A | en_US |
dc.contributor.author | West, MR | en_US |
dc.date.accessioned | 2018-05-15T07:27:50Z | |
dc.date.available | 2018-03-07 | en_US |
dc.date.issued | 2018-03-21 | en_US |
dc.date.submitted | 2018-03-29T11:45:09.800Z | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/38084 | |
dc.description.abstract | TNFα is an important cytokine in inflammatory bowel disease. V565 is a novel anti-TNFα domain antibody developed for oral administration in IBD patients, derived from a llama domain antibody and engineered to enhance intestinal protease resistance. V565 activity was evaluated in TNFα-TNFα receptor-binding ELISAs as well as TNFα responsive cellular assays and demonstrated neutralisation of both soluble and membrane TNFα with potencies similar to those of adalimumab. Although sensitive to pepsin, V565 retained activity after lengthy incubations with trypsin, chymotrypsin, and pancreatin, as well as mouse small intestinal and human ileal and faecal supernatants. In orally dosed naïve and DSS colitis mice, high V565 concentrations were observed in intestinal contents and faeces and immunostaining revealed V565 localisation in mouse colon tissue. V565 was detected by ELISA in post-dose serum of colitis mice, but not naïve mice, demonstrating penetration of disrupted epithelium. In an ex vivo human IBD tissue culture model, V565 inhibition of tissue phosphoprotein levels and production of inflammatory cytokine biomarkers was similar to infliximab, demonstrating efficacy when present at the disease site. Taken together, results of these studies provide confidence that oral V565 dosing will be therapeutic in IBD patients where the mucosal epithelial barrier is compromised. | en_US |
dc.format.extent | 4941 - ? | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Sci Rep | en_US |
dc.rights | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | |
dc.title | Preclinical Development of a Novel, Orally-Administered Anti-Tumour Necrosis Factor Domain Antibody for the Treatment of Inflammatory Bowel Disease. | en_US |
dc.type | Article | |
dc.rights.holder | © The Author(s) 2018 | |
dc.identifier.doi | 10.1038/s41598-018-23277-7 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/29563546 | en_US |
pubs.issue | 1 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 8 | en_US |
dcterms.dateAccepted | 2018-03-07 | en_US |