Nat Commun 2018 Feb 12; 9(1):621
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. Nat Commun 2018 Feb 12; 9(1):621.
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.; Blumberg, Richard S; Sandlie, Inger; and Andersen, Jan Terje, "A human endothelial cell-based recycling assay for screening of FcRn targeted molecules." (2018). Faculty Research 2018. 46.