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Characterization of basigin monoclonal antibodies for receptor-mediated drug delivery to the brain.
- Source :
-
Scientific reports [Sci Rep] 2020 Sep 03; Vol. 10 (1), pp. 14582. Date of Electronic Publication: 2020 Sep 03. - Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- Animals
Antibodies, Monoclonal immunology
Biological Transport
Brain cytology
Cells, Cultured
Endothelial Cells cytology
Endothelial Cells metabolism
Humans
Mice
Transcytosis
Antibodies, Monoclonal metabolism
Basigin immunology
Brain metabolism
Drug Delivery Systems
Epitopes immunology
Pharmaceutical Preparations metabolism
Receptors, Transferrin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 32884039
- Full Text :
- https://doi.org/10.1038/s41598-020-71286-2