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Nat Commun. 2018 Feb 12;9(1):621. doi: 10.1038/s41467-018-03061-x.

A human endothelial cell-based recycling assay for screening of FcRn targeted molecules.

Author information

1
Centre for Immune Regulation (CIR) and Department of Biosciences, University of Oslo, N-0316, Oslo, Norway.
2
CIR and Department of Immunology, Rikshospitalet, Oslo University Hospital and University of Oslo, PO Box 4950, N-0424, Oslo, Norway.
3
Institute of Clinical Medicine, University of Oslo, N-0450 Oslo, Norway.
4
Department of Pathology, Rikshospitalet, Oslo University Hospital and University of Oslo, N-0424, Oslo, Norway.
5
Biochemical and Analytical Research, Large Molecule Research, Roche Pharma Research and Early Development (pRED), Roche Innovation Center, DE-82377 Munich, Germany.
6
School of Pharmacy, University of Oslo, N-0371, Oslo, Norway.
7
Norwegian Institute of Public Health, Infection Immunology, N-0403, Oslo, Norway.
8
Jackson Laboratory, Bar Harbor, ME, 04609, USA.
9
Division of Gastroenterology, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA, 02115, USA.
10
Centre for Immune Regulation (CIR) and Department of Biosciences, University of Oslo, N-0316, Oslo, Norway. j.t.andersen@medisin.uio.no.
11
CIR and Department of Immunology, Rikshospitalet, Oslo University Hospital and University of Oslo, PO Box 4950, N-0424, Oslo, Norway. j.t.andersen@medisin.uio.no.
12
Department of Pharmacology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, N-0424, Oslo, Norway. j.t.andersen@medisin.uio.no.

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.

PMID:
29434196
PMCID:
PMC5809500
DOI:
10.1038/s41467-018-03061-x
[Indexed for MEDLINE]
Free PMC Article

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