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An engineered human Fc domain that behaves like a pH-toggle switch for ultra-long circulation persistence
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Chang-Han | - |
dc.contributor.author | Kang, Tae Hyun | - |
dc.contributor.author | Godon, Ophelie | - |
dc.contributor.author | Watanabe, Makiko | - |
dc.contributor.author | Delidakis, George | - |
dc.contributor.author | Gillis, Caitlin M. | - |
dc.contributor.author | Sterlin, Delphine | - |
dc.contributor.author | Hardy, David | - |
dc.contributor.author | Cogne, Michel | - |
dc.contributor.author | Macdonald, Lynn E. | - |
dc.contributor.author | Murphy, Andrew J. | - |
dc.contributor.author | Tu, Naxin | - |
dc.contributor.author | Lee, Jiwon | - |
dc.contributor.author | McDaniel, Jonathan R. | - |
dc.contributor.author | Makowski, Emily | - |
dc.contributor.author | Tessier, Peter M. | - |
dc.contributor.author | Meyer, Aaron S. | - |
dc.contributor.author | Bruhns, Pierre | - |
dc.contributor.author | Georgiou, George | - |
dc.date.accessioned | 2022-05-04T01:48:54Z | - |
dc.date.available | 2022-05-04T01:48:54Z | - |
dc.date.created | 2020-04-06 | - |
dc.date.created | 2020-04-06 | - |
dc.date.created | 2020-04-06 | - |
dc.date.issued | 2019-11 | - |
dc.identifier.citation | Nature Communications, Vol.10 No.1, p. 5031 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | https://hdl.handle.net/10371/179428 | - |
dc.description.abstract | The pharmacokinetic properties of antibodies are largely dictated by the pH-dependent binding of the IgG fragment crystallizable (Fc) domain to the human neonatal Fc receptor (hFcRn). Engineered Fc domains that confer a longer circulation half-life by virtue of more favorable pH-dependent binding to hFcRn are of great therapeutic interest. Here we developed a pH Toggle switch Fc variant containing the L309D/Q311H/N434S (DHS) substitutions, which exhibits markedly improved pharmacokinetics relative to both native IgG1 and widely used half-life extension variants, both in conventional hFcRn transgenic mice and in new knock-in mouse strains. engineered specifically to recapitulate all the key processes relevant to human antibody persistence in circulation, namely: (i) physiological expression of hFcRn, (ii) the impact of hFc gamma Rs on antibody clearance and (iii) the role of competing endogenous IgG. DHS-IgG retains intact effector functions, which are important for the clearance of target pathogenic cells and also has favorable developability. | - |
dc.language | 영어 | - |
dc.publisher | Nature Publishing Group | - |
dc.title | An engineered human Fc domain that behaves like a pH-toggle switch for ultra-long circulation persistence | - |
dc.type | Article | - |
dc.identifier.doi | 10.1038/s41467-019-13108-2 | - |
dc.citation.journaltitle | Nature Communications | - |
dc.identifier.wosid | 000494635700003 | - |
dc.identifier.scopusid | 2-s2.0-85074624100 | - |
dc.citation.number | 1 | - |
dc.citation.startpage | 5031 | - |
dc.citation.volume | 10 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Lee, Chang-Han | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | EXTENDED HALF-LIFE | - |
dc.subject.keywordPlus | MONOCLONAL-ANTIBODY | - |
dc.subject.keywordPlus | BINDING-PROPERTIES | - |
dc.subject.keywordPlus | GAMMA RECEPTORS | - |
dc.subject.keywordPlus | TRANSGENIC MICE | - |
dc.subject.keywordPlus | HUMAN IGG1 | - |
dc.subject.keywordPlus | AFFINITY | - |
dc.subject.keywordPlus | COMPLEX | - |
dc.subject.keywordPlus | PHARMACOKINETICS | - |
dc.subject.keywordPlus | MOUSE | - |
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