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dc.contributor.authorRoberts, Kevin J
dc.contributor.authorCubitt, Marion F
dc.contributor.authorCarlton, Timothy M
dc.contributor.authorRodrigues-Duarte, Lurdes
dc.contributor.authorMaggiore, Luana
dc.contributor.authorChai, Ray
dc.contributor.authorClare, Simon
dc.contributor.authorHarcourt, Katherine
dc.contributor.authorMacDonald, Thomas T
dc.contributor.authorRay, Keith P
dc.contributor.authorVossenkämper, Anna
dc.contributor.authorWest, Michael R
dc.contributor.authorCrowe, J Scott
dc.date.accessioned2021-11-02T00:30:19Z
dc.date.available2021-11-02T00:30:19Z
dc.date.issued2021-09-30
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330154
dc.description.abstractAnti-TNFα and anti-IL-23 antibodies are highly effective therapies for Crohn's disease or ulcerative colitis in a proportion of patients. V56B2 is a novel bispecific domain antibody in which a llama-derived IL-23p19-specific domain antibody, humanised and engineered for intestinal protease resistance, V900, was combined with a previously-described TNFα-specific domain antibody, V565. V56B2 contains a central protease-labile linker to create a single molecule for oral administration. Incubation of V56B2 with trypsin or human faecal supernatant resulted in a complete separation of the V565 and V900 monomers without loss of neutralising potency. Following oral administration of V900 and V565 in mice, high levels of each domain antibody were detected in the faeces, demonstrating stability in the intestinal milieu. In ex vivo cultures of colonic biopsies from IBD patients, treatment with V565 or V900 inhibited tissue phosphoprotein levels and with a combination of the two, inhibition was even greater. These results support further development of V56B2 as an oral therapy for IBD with improved safety and efficacy in a greater proportion of patients as well as greater convenience for patients compared with traditional monoclonal antibody therapies.
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titlePreclinical development of a bispecific TNFα/IL-23 neutralising domain antibody as a novel oral treatment for inflammatory bowel disease.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2021
prism.publicationNameSci Rep
prism.startingPage19422
prism.volume11
dc.identifier.doi10.17863/CAM.77597
dcterms.dateAccepted2021-08-10
rioxxterms.versionofrecord10.1038/s41598-021-97236-0
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-09-30
dc.identifier.eissn2045-2322
rioxxterms.typeJournal Article/Review
cam.issuedOnline2021-09-30


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International