Subcellular trafficking and transcytosis efficacy of different receptor types for therapeutic antibody delivery at the blood‒brain barrier

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  • Mikkel Roland Holst
  • Nienke Marije de Wit
  • Ozgür, Burak
  • Andreas Brachner
  • Kathrine Hyldig
  • Antje Appelt-Menzel
  • Hannah Sleven
  • Zameel Cader
  • Helga Eveline de Vries
  • Winfried Neuhaus
  • Allan Jensen
  • Larsen, Birger Brodin
  • Morten Schallburg Nielsen

Here, we report an experimental setup to benchmark different receptors for targeted therapeutic antibody delivery at the blood–brain barrier. We used brain capillary endothelial-like cells derived from induced pluripotent stem cells (hiPSC-BECs) as a model system and compared them to colon epithelial Caco-2 cells. This approach helped to identify favourable receptors for transport into the cell layer itself or for directing transport for transcytosis across the cell layer. The sorting receptors transferrin receptor and sortilin were shown to be efficient as antibody cargo receptors for intracellular delivery to the cell layer. In contrast, the cell surface receptors CD133 and podocalyxin were identified as static and inefficient receptors for delivering cargo antibodies. Similar to in vivo studies, the hiPSC-BECs maintained detectable transcytotic transport via transferrin receptor, while transcytosis was restricted using sortilin as a cargo receptor. Based on these findings, we propose the application of sortilin as a cargo receptor for delivering therapeutic antibodies into the brain microvascular endothelium. Graphical Abstract: [Figure not available: see fulltext.]

Original languageEnglish
Article number82
JournalFluids and Barriers of the CNS
Issue number1
Number of pages17
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

    Research areas

  • Blood‒brain barrier, Brain endothelial cells, Caco-2, Cargo receptor, CD133, Podocalyxin, Receptor-mediated transcytosis, Sortilin, Therapeutic antibodies, Transcytosis, Transferrin receptor

ID: 373612265