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

Algirdas Grevys, Jeannette Nilsen, Kine M. K. Sand, Muluneh B. Daba, Inger Øynebråten, Malin Bern, Martin B. McAdam, Stian Foss, Tilman Schlothauer, Terje E. Michaelsen, Gregory J. Christianson, Derry C. Roopenian, Richard S. Blumberg, Inger Sandlie and Jan Terje Andersen ()
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Algirdas Grevys: University of Oslo
Jeannette Nilsen: Rikshospitalet, Oslo University Hospital and University of Oslo
Kine M. K. Sand: University of Oslo
Muluneh B. Daba: University of Oslo
Inger Øynebråten: Oslo University Hospital and University of Oslo
Malin Bern: University of Oslo
Martin B. McAdam: University of Oslo
Stian Foss: University of Oslo
Tilman Schlothauer: Roche Innovation Center
Terje E. Michaelsen: University of Oslo
Gregory J. Christianson: Jackson Laboratory
Derry C. Roopenian: Jackson Laboratory
Richard S. Blumberg: Harvard Medical School
Inger Sandlie: University of Oslo
Jan Terje Andersen: University of Oslo

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03061-x

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