Preclinical development of a bispecific TNFα/IL-23 neutralising domain antibody as a novel oral treatment for inflammatory bowel disease.
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Authors
Roberts, Kevin J
Cubitt, Marion F
Carlton, Timothy M
Rodrigues-Duarte, Lurdes
Maggiore, Luana
Chai, Ray
Clare, Simon
Harcourt, Katherine
MacDonald, Thomas T
Ray, Keith P
Vossenkämper, Anna
West, Michael R
Crowe, J Scott
Publication Date
2021-09-30Journal Title
Sci Rep
ISSN
2045-2322
Publisher
Springer Science and Business Media LLC
Volume
11
Issue
1
Pages
19422
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic
Metadata
Show full item recordCitation
Roberts, K. J., Cubitt, M. F., Carlton, T. M., Rodrigues-Duarte, L., Maggiore, L., Chai, R., Clare, S., et al. (2021). Preclinical development of a bispecific TNFα/IL-23 neutralising domain antibody as a novel oral treatment for inflammatory bowel disease.. Sci Rep, 11 (1), 19422. https://doi.org/10.1038/s41598-021-97236-0
Abstract
Anti-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.
Identifiers
External DOI: https://doi.org/10.1038/s41598-021-97236-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330154
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