dc.date.accessioned | 2022-10-25T15:29:47Z | |
dc.date.available | 2022-10-25T15:29:47Z | |
dc.date.created | 2022-09-03T13:00:52Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Tollefsrud Gjølberg, Torleif Frick, Rahel Mester, Simone Foss, Stian Grevys, Algirdas Høydahl, Lene Støkken Jørstad, Øystein Kalsnes Schlothauer, Tilman Sandlie, Inger Moe, Morten Carsten Andersen, Jan Terje . Biophysical differences in IgG1 Fc-based therapeutics relate to their cellular handling, interaction with FcRn and plasma half-life. Communications Biology. 2022, 5(1), 1-17 | |
dc.identifier.uri | http://hdl.handle.net/10852/97295 | |
dc.description.abstract | Abstract Antibody-based therapeutics (ABTs) are used to treat a range of diseases. Most ABTs are either full-length IgG1 antibodies or fusions between for instance antigen (Ag)-binding receptor domains and the IgG1 Fc fragment. Interestingly, their plasma half-life varies considerably, which may relate to how they engage the neonatal Fc receptor (FcRn). As such, there is a need for an in-depth understanding of how different features of ABTs affect FcRn-binding and transport behavior. Here, we report on how FcRn-engagement of the IgG1 Fc fragment compare to clinically relevant IgGs and receptor domain Fc fusions, binding to VEGF or TNF-α. The results reveal FcRn-dependent intracellular accumulation of the Fc, which is in line with shorter plasma half-life than that of full-length IgG1 in human FcRn-expressing mice. Receptor domain fusion to the Fc increases its half-life, but not to the extent of IgG1. This is mirrored by a reduced cellular recycling capacity of the Fc-fusions. In addition, binding of cognate Ag to ABTs show that complexes of similar size undergo cellular transport at different rates, which could be explained by the biophysical properties of each ABT. Thus, the study provides knowledge that should guide tailoring of ABTs regarding optimal cellular sorting and plasma half-life. | |
dc.language | EN | |
dc.publisher | Nature Portfolio | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Biophysical differences in IgG1 Fc-based therapeutics relate to their cellular handling, interaction with FcRn and plasma half-life | |
dc.title.alternative | ENEngelskEnglishBiophysical differences in IgG1 Fc-based therapeutics relate to their cellular handling, interaction with FcRn and plasma half-life | |
dc.type | Journal article | |
dc.creator.author | Tollefsrud Gjølberg, Torleif | |
dc.creator.author | Frick, Rahel | |
dc.creator.author | Mester, Simone | |
dc.creator.author | Foss, Stian | |
dc.creator.author | Grevys, Algirdas | |
dc.creator.author | Høydahl, Lene Støkken | |
dc.creator.author | Jørstad, Øystein Kalsnes | |
dc.creator.author | Schlothauer, Tilman | |
dc.creator.author | Sandlie, Inger | |
dc.creator.author | Moe, Morten Carsten | |
dc.creator.author | Andersen, Jan Terje | |
cristin.unitcode | 185,53,43,11 | |
cristin.unitname | Øyeavdelingen | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 2048557 | |
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=Communications Biology&rft.volume=5&rft.spage=1&rft.date=2022 | |
dc.identifier.jtitle | Communications Biology | |
dc.identifier.volume | 5 | |
dc.identifier.issue | 1 | |
dc.identifier.doi | https://doi.org/10.1038/s42003-022-03787-x | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 2399-3642 | |
dc.type.version | PublishedVersion | |
cristin.articleid | 832 | |