Human FcRn Tissue Expression Profile and Half-Life in PBMCs

Abstract

System-wide quantitative characterization of human neonatal Fc receptor (FcRn) properties is critical for understanding and predicting human PK (pharmacokinetics) as well as the distribution of mAbs and Fc-fusion proteins using PBPK (physiologically-based pharmacokinetic) modeling. To this end, tissue-specific FcRn expression and half-life are important model inputs. Herein, human FcRn tissue expression was measured by peptide immunoaffinity chromatography coupled with high-resolution mass spectrometry. FcRn concentrations across 14 human tissues ranged from low to 230 pmol per gram of tissue. Furthermore, the FcRn half-life was determined to be 11.1 h from a human stable isotope labelled leucine pulse labeling experiment. The spatial and temporal quantitative human FcRn data now promise to enable a refined PBPK model with improved accuracy of human PK predictions for Fc-containing biotherapeutics.

Keywords

• antibody
• human FcRn
• half-life
• IA-LC-HRMS
• tissue-based target quantification
• PBPK