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

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Characterization of basigin monoclonal antibodies for receptor-mediated drug delivery to the brain. / Christensen, Sarah Christine; Krogh, Berit Olsen; Jensen, Allan; Andersen, Christian Brix Folsted; Christensen, Søren; Nielsen, Morten Schallburg.

In: Scientific Reports, Vol. 10, No. 1, 14582, 2020.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Christensen, Sarah Christine ; Krogh, Berit Olsen ; Jensen, Allan ; Andersen, Christian Brix Folsted ; Christensen, Søren ; Nielsen, Morten Schallburg. / Characterization of basigin monoclonal antibodies for receptor-mediated drug delivery to the brain. In: Scientific Reports. 2020 ; Vol. 10, No. 1.

Bibtex

@article{c809bca244734a5388022bb23a0dd391,
title = "Characterization of basigin monoclonal antibodies for receptor-mediated drug delivery to the brain",
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.",
author = "Christensen, {Sarah Christine} and Krogh, {Berit Olsen} and Allan Jensen and Andersen, {Christian Brix Folsted} and S{\o}ren Christensen and Nielsen, {Morten Schallburg}",
year = "2020",
doi = "10.1038/s41598-020-71286-2",
language = "English",
volume = "10",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Characterization of basigin monoclonal antibodies for receptor-mediated drug delivery to the brain

AU - Christensen, Sarah Christine

AU - Krogh, Berit Olsen

AU - Jensen, Allan

AU - Andersen, Christian Brix Folsted

AU - Christensen, Søren

AU - Nielsen, Morten Schallburg

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-020-71286-2

DO - 10.1038/s41598-020-71286-2

M3 - Journal article

C2 - 32884039

VL - 10

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 14582

ER -