A human endothelial cell-based recycling assay for screening of FcRn targeted molecules
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Author
Grevys, Algirdas
Nilsen, Jeannette
Sand, Kine M. K.
Daba, Muluneh B.
Øynebråten, Inger
Bern, Malin
McAdam, Martin B.
Foss, Stian
Schlothauer, Tilman
Michaelsen, Terje E.
Christianson, Gregory J.
Roopenian, Derry C.
Sandlie, Inger
Andersen, Jan Terje
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1038/s41467-018-03061-xMetadata
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Grevys, A., J. Nilsen, K. M. K. Sand, M. B. Daba, I. Øynebråten, M. Bern, M. B. McAdam, et al. 2018. “A human endothelial cell-based recycling assay for screening of FcRn targeted molecules.” Nature Communications 9 (1): 621. doi:10.1038/s41467-018-03061-x. http://dx.doi.org/10.1038/s41467-018-03061-x.Abstract
Albumin and IgG have remarkably long serum half-lives due to pH-dependent FcRn-mediated cellular recycling that rescues both ligands from intracellular degradation. Furthermore, increase in half-lives of IgG and albumin-based therapeutics has the potential to improve their efficacies, but there is a great need for robust methods for screening of relative FcRn-dependent recycling ability. Here, we report on a novel human endothelial cell-based recycling assay (HERA) that can be used for such pre-clinical screening. In HERA, rescue from degradation depends on FcRn, and engineered ligands are recycled in a manner that correlates with their half-lives in human FcRn transgenic mice. Thus, HERA is a novel cellular assay that can be used to predict how FcRn-binding proteins are rescued from intracellular degradation.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809500/pdf/Terms of Use
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http://nrs.harvard.edu/urn-3:HUL.InstRepos:35014420
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