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

Author

Listed:
  • Algirdas Grevys

    (University of Oslo
    Rikshospitalet, Oslo University Hospital and University of Oslo)

  • Jeannette Nilsen

    (Rikshospitalet, Oslo University Hospital and University of Oslo
    University of Oslo)

  • Kine M. K. Sand

    (University of Oslo
    Rikshospitalet, Oslo University Hospital and University of Oslo)

  • Muluneh B. Daba

    (University of Oslo
    Rikshospitalet, Oslo University Hospital and University of Oslo)

  • Inger Øynebråten

    (Oslo University Hospital and University of Oslo)

  • Malin Bern

    (University of Oslo
    Rikshospitalet, Oslo University Hospital and University of Oslo)

  • Martin B. McAdam

    (University of Oslo
    Rikshospitalet, Oslo University Hospital and University of Oslo)

  • Stian Foss

    (University of Oslo
    Rikshospitalet, Oslo University Hospital and University of Oslo)

  • Tilman Schlothauer

    (Roche Innovation Center)

  • Terje E. Michaelsen

    (University of Oslo
    Norwegian Institute of Public Health, Infection Immunology)

  • Gregory J. Christianson

    (Jackson Laboratory)

  • Derry C. Roopenian

    (Jackson Laboratory)

  • Richard S. Blumberg

    (Harvard Medical School)

  • Inger Sandlie

    (University of Oslo
    Rikshospitalet, Oslo University Hospital and University of Oslo)

  • Jan Terje Andersen

    (University of Oslo
    Rikshospitalet, Oslo University Hospital and University of Oslo
    University of Oslo and Oslo University Hospital)

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.

Suggested Citation

  • 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. Christian, 2018. "A human endothelial cell-based recycling assay for screening of FcRn targeted molecules," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03061-x
    DOI: 10.1038/s41467-018-03061-x
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    Cited by:

    1. Torleif Tollefsrud Gjølberg & Jonas Aakre Wik & Hanna Johannessen & Stig Krüger & Nicola Bassi & Panagiotis F. Christopoulos & Malin Bern & Stian Foss & Goran Petrovski & Morten C. Moe & Guttorm Haral, 2023. "Antibody blockade of Jagged1 attenuates choroidal neovascularization," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Stian Foss & Siri A. Sakya & Leire Aguinagalde & Marta Lustig & Jutamas Shaughnessy & Ana Rita Cruz & Lisette Scheepmaker & Line Mathiesen & Fulgencio Ruso-Julve & Aina Karen Anthi & Torleif Tollefsru, 2024. "Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Maximilian Brinkhaus & Erwin Pannecoucke & Elvera J. Kooi & Arthur E. H. Bentlage & Ninotska I. L. Derksen & Julie Andries & Bianca Balbino & Magdalena Sips & Peter Ulrichts & Peter Verheesen & Hans H, 2022. "The Fab region of IgG impairs the internalization pathway of FcRn upon Fc engagement," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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