A Cell-Based FcRn-dependent Recycling assay for Predictive Pharmacokinetic assessment of Therapeutic Antibodies
Abstract
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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The Fab portion of IgGs and subtle differences in complementarity-determining region sequence can impact interactions of IgG with FcRn.
“it has been demonstrated that the Fab portion of IgGs, and even subtle differences in complementarity-determining region sequence, can impact on interactions of IgG with this receptor [30–34].”
From The uptake, intracellular trafficking and recycling of FcRn-blocking therapeutics in human endothelial cells in vitro (2026) · cites this paper as [33]
Cites
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Sirina, J., D'Hooghe, L. E., Singhvi-Hanns, L. A., Cole, S. L., Shock, A., Holliday, N. D., & Stoddart, L. A. (2026) · Cellular Immunology · doi:10.1016/j.cellimm.2026.105128
- Authors
- Liu, C., Kim, Y. S., Lowe, J. H.-N., & Chung, S.
- Affiliations
- Genentech (US)
- Venue
- Bioanalysis
- Publisher
- Informa UK Limited
- Published
- 2021-07
- Volume
- 13
- Issue
- 14
- Pages
- 1135-1144
- ISSN
- 1757-6180 (ISSN-L)
- 1757-6199
- OpenAlex
- W3185941090
- Cited by
- 8
- References
- 6
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2021: 1
- FWCI
- 0.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bioanalysis (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Genentech
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Keywords
- neonatal Fc receptor, antibody recycling, pharmacokinetics, therapeutic monoclonal antibodies, IgG half-life, lysosomal degradation, transwell culture, cell-based assays, antibody clearance, biologic therapy
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