4.3 Article

A cell-based FcRn-dependent recycling assay for predictive pharmacokinetic assessment of therapeutic antibodies

Journal

BIOANALYSIS
Volume 13, Issue 14, Pages 1135-1144

Publisher

Newlands Press Ltd
DOI: 10.4155/bio-2021-0099

Keywords

biotherapeutics; cell-based assay; FcRn; pharmacokinetics; recycling

Funding

  1. Genentech, Inc.

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This study developed a novel cell-based assay for quantifying the recycling of monoclonal antibodies, showing a strong correlation between the assay output and clearance in humans, suggesting its potential application as a pharmacokinetic prescreening tool for IgG-based candidate therapeutic monoclonal antibodies.
Aim: Evaluation of suitable pharmacokinetic properties is critical for successful development of IgG-based biotherapeutics. The prolonged half-lives of IgGs depend on the intracellular trafficking function of neonatal Fc receptor, which rescues internalized IgGs from lysosomal degradation and recycles them back to circulation. Results: Here, we developed a novel cell-based assay to quantify recycling of monoclonal antibodies in a transwell culture system that uses a cell line that stably expresses human neonatal Fc receptor. We tested seven therapeutic antibodies and showed that the recycling output of the assay strongly correlated with the clearance in humans. Conclusion: This recycling assay has potential application as a pharmacokinetic prescreening tool to facilitate development and selection of IgG-based candidate therapeutic monoclonal antibodies.

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