Characterization of basigin monoclonal antibodies for receptor-mediated drug delivery to the brain

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DOI

The brain uptake of biotherapeutics for brain diseases is hindered by the blood-brain barrier (BBB). The BBB selectively regulates the transport of large molecules into the brain and thereby maintains brain homeostasis. Receptor-mediated transcytosis (RMT) is one mechanism to deliver essential proteins into the brain parenchyma. Receptors expressed in the brain endothelial cells have been explored to ferry therapeutic antibodies across the BBB in bifunctional antibody formats. In this study, we generated and characterized monoclonal antibodies (mAbs) binding to the basigin receptor, which recently has been proposed as a target for RMT across the BBB. Antibody binding properties such as affinity have been demonstrated to be important factors for transcytosis capability and efficiency. Nevertheless, studies of basigin mAb properties' effect on RMT are limited. Here we characterize different basigin mAbs for their ability to associate with and subsequently internalize human brain endothelial cells. The mAbs were profiled to determine whether receptor binding epitope and affinity affected receptor-mediated uptake efficiency. By competitive epitope binning studies, basigin mAbs were categorized into five epitope bins. mAbs from three of the epitope bins demonstrated properties required for RMT candidates judged by binding characteristics and their superior level of internalization in human brain endothelial cells.

OriginalsprogEngelsk
Artikelnummer14582
TidsskriftScientific Reports
Vol/bind10
Nummer1
Antal sider13
ISSN2045-2322
DOI
StatusUdgivet - 2020

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