Fab-dsFv: A bispecific antibody format with extended serum half-life through albumin binding
| Autor: | Alastair D. G. Lawson, Ralph Adams, Joanne E. Compson, Tim Kopotsha, Michael Airey, Hanna Hailu, David Paul Humphreys, Oliver Zaccheo, Kaushik Sarkar, Mark Jairaj, Wild Gavin Barry, Andrew M. Ventom, Sarah L. Dugdale, Louis Christodoulou, Emma Dave, Sarah Malcolm, Diane Marshall, Alison Turner, Bruce Carrington, James T. Heads, Miren Zamacona, Sam Philip Heywood |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Stereochemistry Immunology Serum albumin Fc receptor Immunoglobulin Variable Region Peptide 03 medical and health sciences Anti-albumin serum half-life Immunoglobulin Fab Fragments Mice 0302 clinical medicine Antigen In vivo Report Antibodies Bispecific medicine Immunology and Allergy Animals Humans Fab Serum Albumin chemistry.chemical_classification biology Human serum albumin Molecular biology FcRn 030104 developmental biology chemistry human serum albumin 030220 oncology & carcinogenesis anti-albumin Fv biology.protein Antibody medicine.drug Half-Life |
| Zdroj: | mAbs |
| ISSN: | 1942-0870 1942-0862 |
| Popis: | An antibody format, termed Fab-dsFv, has been designed for clinical indications that require monovalent target binding in the absence of direct Fc receptor (FcR) binding while retaining substantial serum presence. The variable fragment (Fv) domain of a humanized albumin-binding antibody was fused to the C-termini of Fab constant domains, such that the VL and VH domains were individually connected to the Cκ and CH1 domains by peptide linkers, respectively. The anti-albumin Fv was selected for properties thought to be desirable to ensure a durable serum half-life mediated via FcRn. The Fv domain was further stabilized by an inter-domain disulfide bond. The bispecific format was shown to be thermodynamically and biophysically stable, and retained good affinity and efficacy to both antigens simultaneously. In in vivo studies, the serum half-life of Fab-dsFv, 2.6 d in mice and 7.9 d in cynomolgus monkeys, was equivalent to Fab'-PEG. |
| Databáze: | OpenAIRE |
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