dc.date.accessioned | 2021-10-04T15:54:14Z | |
dc.date.available | 2021-10-04T15:54:14Z | |
dc.date.created | 2021-09-16T16:00:29Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Mester, Simone Evers, Mitchell Meyer, Saskia Nilsen, Jeannette Greiff, Victor Sandlie, Inger Leusen, Jeanette Andersen, Jan Terje . Extended plasma half-life of albumin-binding domain fused human IgA upon pH-dependent albumin engagement of human FcRn in vitro and in vivo. mAbs. 2021, 13:1893888(1), 1-14 | |
dc.identifier.uri | http://hdl.handle.net/10852/88732 | |
dc.description.abstract | Albumin has a serum half-life of 3 weeks in humans. This feature can be used to improve the pharmacokinetics of shorter-lived biologics. For instance, an albumin-binding domain (ABD) can be used to recruit albumin. A prerequisite for such design is that the ABD-albumin interaction does not interfere with pH-dependent binding of albumin to the human neonatal Fc receptor (FcRn), as FcRn acts as the principal regulator of the half-life of albumin. Thus, there is a need to know how ABDs act in the context of fusion partners and human FcRn. Here, we studied the binding and transport properties of human immunoglobulin A1 (IgA1), fused to a Streptococcus protein G-derived engineered ABD, in in vitro and in vivo systems harboring human FcRn. IgA has great potential as a therapeutic protein, but its short half-life is a major drawback. We demonstrate that ABD-fused IgA1 binds human FcRn pH-dependently and is rescued from cellular degradation in a receptor-specific manner in the presence of albumin. This occurs when ABD is fused to either the light or the heavy chain. In human FcRn transgenic mice, IgA1-ABD in complex with human albumin, gave 4-6-fold extended half-life compared to unmodified IgA1, where the light chain fusion showed the longest half-life. When the heavy chain-fused protein was pre-incubated with an engineered human albumin with improved FcRn binding, cellular rescue and half-life was further enhanced. Our study reveals how an ABD, which does not interfere with albumin binding to human FcRn, may be used to extend the half-life of IgA. | |
dc.language | EN | |
dc.rights | Attribution-NonCommercial 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0/ | |
dc.title | Extended plasma half-life of albumin-binding domain fused human IgA upon pH-dependent albumin engagement of human FcRn in vitro and in vivo | |
dc.type | Journal article | |
dc.creator.author | Mester, Simone | |
dc.creator.author | Evers, Mitchell | |
dc.creator.author | Meyer, Saskia | |
dc.creator.author | Nilsen, Jeannette | |
dc.creator.author | Greiff, Victor | |
dc.creator.author | Sandlie, Inger | |
dc.creator.author | Leusen, Jeanette | |
dc.creator.author | Andersen, Jan Terje | |
cristin.unitcode | 185,15,29,60 | |
cristin.unitname | Genetikk og evolusjonsbiologi | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1935058 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=mAbs&rft.volume=13:1893888&rft.spage=1&rft.date=2021 | |
dc.identifier.jtitle | mAbs | |
dc.identifier.volume | 13 | |
dc.identifier.issue | 1 | |
dc.identifier.doi | https://doi.org/10.1080/19420862.2021.1893888 | |
dc.identifier.urn | URN:NBN:no-91349 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 1942-0862 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/88732/1/Postnr%2B1935058_Mester%2Bet%2Bal_mAbs_Article%2B1893888%2B2021.pdf | |
dc.type.version | PublishedVersion | |
cristin.articleid | 1893888 | |
dc.relation.project | NFR/179573 | |
dc.relation.project | NFR/230526 | |
dc.relation.project | EC/H2020/825821 | |
dc.relation.project | NFR/287927 | |
dc.relation.project | NFR/300740 | |
dc.relation.project | HSØ/40018 | |