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

Research output: Contribution to journal › Journal article › Research › peer-review

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Subcellular trafficking and transcytosis efficacy of different receptor types for therapeutic antibody delivery at the blood‒brain barrier. / Holst, Mikkel Roland; de Wit, Nienke Marije; Ozgür, Burak; Brachner, Andreas; Hyldig, Kathrine; Appelt-Menzel, Antje; Sleven, Hannah; Cader, Zameel; de Vries, Helga Eveline; Neuhaus, Winfried; Jensen, Allan; Brodin, Birger; Nielsen, Morten Schallburg.

In: Fluids and Barriers of the CNS, Vol. 20, No. 1, 82, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Holst, MR, de Wit, NM, Ozgür, B, Brachner, A, Hyldig, K, Appelt-Menzel, A, Sleven, H, Cader, Z, de Vries, HE, Neuhaus, W, Jensen, A, Brodin, B & Nielsen, MS 2023, 'Subcellular trafficking and transcytosis efficacy of different receptor types for therapeutic antibody delivery at the blood‒brain barrier', Fluids and Barriers of the CNS, vol. 20, no. 1, 82. https://doi.org/10.1186/s12987-023-00480-x

APA

Holst, M. R., de Wit, N. M., Ozgür, B., Brachner, A., Hyldig, K., Appelt-Menzel, A., Sleven, H., Cader, Z., de Vries, H. E., Neuhaus, W., Jensen, A., Brodin, B., & Nielsen, M. S. (2023). Subcellular trafficking and transcytosis efficacy of different receptor types for therapeutic antibody delivery at the blood‒brain barrier. Fluids and Barriers of the CNS, 20(1), [82]. https://doi.org/10.1186/s12987-023-00480-x

Vancouver

Holst MR, de Wit NM, Ozgür B, Brachner A, Hyldig K, Appelt-Menzel A et al. Subcellular trafficking and transcytosis efficacy of different receptor types for therapeutic antibody delivery at the blood‒brain barrier. Fluids and Barriers of the CNS. 2023;20(1). 82. https://doi.org/10.1186/s12987-023-00480-x

Author

Holst, Mikkel Roland ; de Wit, Nienke Marije ; Ozgür, Burak ; Brachner, Andreas ; Hyldig, Kathrine ; Appelt-Menzel, Antje ; Sleven, Hannah ; Cader, Zameel ; de Vries, Helga Eveline ; Neuhaus, Winfried ; Jensen, Allan ; Brodin, Birger ; Nielsen, Morten Schallburg. / Subcellular trafficking and transcytosis efficacy of different receptor types for therapeutic antibody delivery at the blood‒brain barrier. In: Fluids and Barriers of the CNS. 2023 ; Vol. 20, No. 1.

Bibtex

@article{15905916522344669fecdc15d4e1916e,

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

abstract = "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.]",

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

author = "Holst, {Mikkel Roland} and {de Wit}, {Nienke Marije} and Burak Ozg{\"u}r and Andreas Brachner and Kathrine Hyldig and Antje Appelt-Menzel and Hannah Sleven and Zameel Cader and {de Vries}, {Helga Eveline} and Winfried Neuhaus and Allan Jensen and Birger Brodin and Nielsen, {Morten Schallburg}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

doi = "10.1186/s12987-023-00480-x",

language = "English",

volume = "20",

journal = "Fluids and Barriers of the CNS",

issn = "2045-8118",

publisher = "BioMed Central Ltd.",

number = "1",

}

RIS

TY - JOUR

T1 - Subcellular trafficking and transcytosis efficacy of different receptor types for therapeutic antibody delivery at the blood‒brain barrier

AU - Holst, Mikkel Roland

AU - de Wit, Nienke Marije

AU - Ozgür, Burak

AU - Brachner, Andreas

AU - Hyldig, Kathrine

AU - Appelt-Menzel, Antje

AU - Sleven, Hannah

AU - Cader, Zameel

AU - de Vries, Helga Eveline

AU - Neuhaus, Winfried

AU - Jensen, Allan

AU - Brodin, Birger

AU - Nielsen, Morten Schallburg

PY - 2023

Y1 - 2023

N2 - 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.]

AB - 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.]

KW - Blood‒brain barrier

KW - Brain endothelial cells

KW - Caco-2

KW - Cargo receptor

KW - CD133

KW - Podocalyxin

KW - Receptor-mediated transcytosis

KW - Sortilin

KW - Therapeutic antibodies

KW - Transcytosis

KW - Transferrin receptor

U2 - 10.1186/s12987-023-00480-x

DO - 10.1186/s12987-023-00480-x

M3 - Journal article

C2 - 37932749

AN - SCOPUS:85175824172

VL - 20

JO - Fluids and Barriers of the CNS

JF - Fluids and Barriers of the CNS

SN - 2045-8118

IS - 1

M1 - 82

ER -

ID: 373612265

Department of Pharmacy