Characterization of basigin monoclonal antibodies for receptor-mediated drug delivery to the brain.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
03 09 2020
03 09 2020
Historique:
received:
14
04
2020
accepted:
05
08
2020
entrez:
5
9
2020
pubmed:
5
9
2020
medline:
26
3
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32884039
doi: 10.1038/s41598-020-71286-2
pii: 10.1038/s41598-020-71286-2
pmc: PMC7471916
doi:
Substances chimiques
Antibodies, Monoclonal
0
Epitopes
0
Pharmaceutical Preparations
0
Receptors, Transferrin
0
Basigin
136894-56-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14582Références
Zuchero, Y. J. Y. et al. Discovery of novel blood-brain barrier targets to enhance brain uptake of therapeutic antibodies. Neuron 89, 70–82 (2016).
doi: 10.1016/j.neuron.2015.11.024
Yu, Y. J. et al. Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target. Sci. Transl. Med. 3, 84ra44 (2011).
doi: 10.1126/scitranslmed.3002230
Fishman, J. B., Rubin, J. B., Handrahan, J. V., Connor, J. R. & Fine, R. E. Receptor-mediated transcytosis of transferrin across the blood-brain barrier. J. Neurosci. Res. 18, 299–304 (1987).
doi: 10.1002/jnr.490180206
Couch, J. A. et al. Addressing safety liabilities of TfR bispecific antibodies that cross the blood-brain barrier. Sci. Transl. Med. 5(183ra57), 1–12 (2013).
Pardridge, W. M., Boado, R. J., Patrick, D. J., Ka-Wai Hui, E. & Lu, J. Z. Blood-brain barrier transport, plasma pharmacokinetics, and neuropathology following chronic treatment of the rhesus monkey with a brain penetrating humanized monoclonal antibody against the human transferrin receptor. Mol. Pharm. 15, 5207–5216 (2018).
doi: 10.1021/acs.molpharmaceut.8b00730
Weber, F. et al. Brain shuttle antibody for Alzheimer’s disease with attenuated peripheral effector function due to an inverted binding mode. Cell Rep. 22, 149–162 (2018).
doi: 10.1016/j.celrep.2017.12.019
Sun, J., Boado, R. J., Pardridge, W. M. & Sumbria, R. K. Plasma pharmacokinetics of high-affinity transferrin receptor antibody-erythropoietin fusion protein is a function of effector attenuation in mice. Mol. Pharm. 16, 3534–3543 (2019).
doi: 10.1021/acs.molpharmaceut.9b00369
Sharma, K. et al. Cell type- and brain region-resolved mouse brain proteome. Nat. Neurosci. 18, 1819–1831 (2015).
doi: 10.1038/nn.4160
Miyauchi, T. et al. Basigin, a new, broadly distributed member of the immunoglobulin superfamily, has strong homology with both the immunoglobulin v domain and the β-chain of major histocompatibility complex class ii antigen. J. Biochem. 107, 316–323 (1990).
doi: 10.1093/oxfordjournals.jbchem.a123045
Biswas, C. Tumor cell stimulation of collagenase production by fibroblasts. Biochem. Biophys. Res. Commun. 109, 1026–1034 (1982).
doi: 10.1016/0006-291X(82)92042-3
Tam, S. J. et al. Death receptors DR6 and TROY regulate brain vascular development. Dev. Cell 22, 403–417 (2012).
doi: 10.1016/j.devcel.2011.11.018
Zhang, Y. & Pardridge, W. M. Delivery of β-galactosidase to mouse brain via the blood–brain barrier transferrin receptor. J. Pharmacol. Exp. Ther. 313, 1075–1081 (2005).
doi: 10.1124/jpet.104.082974
Burggraf, D. et al. Matrix metalloproteinase induction by EMMPRIN in experimental focal cerebral ischemia. Eur. J. Neurosci. 22, 273–277 (2005).
doi: 10.1111/j.1460-9568.2005.04187.x
Agrawal, S. M., Silva, C., Tourtellotte, W. W. & Yong, V. W. EMMPRIN: a novel regulator of leukocyte transmigration into the CNS in multiple sclerosis and experimental autoimmune encephalomyelitis. J. Neurosci. 31, 669–677 (2011).
doi: 10.1523/JNEUROSCI.3659-10.2011
Nahalkova, J. et al. CD147, a gamma-secretase associated protein is upregulated in Alzheimer’s disease brain and its cellular trafficking is affected by presenilin-2. Neurochem. Int. 56, 67–76 (2010).
doi: 10.1016/j.neuint.2009.09.003
Muramatsu, T. Basigin (CD147), a multifunctional transmembrane glycoprotein with various binding partners. J. Biochem. 159, 481–490 (2016).
doi: 10.1093/jb/mvv127
Yu, X.-L. et al. Crystal structure of HAb18G/CD147. J. Biol. Chem. 283, 18056–18065 (2008).
doi: 10.1074/jbc.M802694200
Muramatsu, T. & Miyauchi, T. Basigin (CD147): a multifunctional transmembrane protein involved in reproduction, neural function, inflammation and tumor invasion. Histol. Histopathol. 18, 981–987 (2003).
pubmed: 12792908
Biswas, C. et al. The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer Res. 55, 434–439 (1995).
pubmed: 7812975
Miyauchi, T., Masuzawa, Y. & Muramatsu, T. The basigin group of the immunoglobulin superfamily: complete conservation of a segment in and around transmembrane domains of human and mouse basigin and chicken HT7 antigen. J. Biochem. 110, 770–774 (1991).
doi: 10.1093/oxfordjournals.jbchem.a123657
Tang, W. & Hemler, M. E. Caveolin-1 regulates matrix metalloproteinases-1 induction and CD147/EMMPRIN cell surface clustering. J. Biol. Chem. 279, 11112–11118 (2004).
doi: 10.1074/jbc.M312947200
Huang, W. et al. Modulation of CD147-induced matrix metalloproteinase activity: role of CD147 N-glycosylation. Biochem. J. 449, 437–448 (2013).
doi: 10.1042/BJ20120343
Tang, W., Chang, S. B. & Hemler, M. E. Links between CD147 function, glycosylation, and caveolin-1. Mol. Biol. Cell 15, 4043–4050 (2004).
doi: 10.1091/mbc.e04-05-0402
Bai, Y., Huang, W., Ma, L.-T., Jiang, J.-L. & Chen, Z.-N. Importance of N-glycosylation on CD147 for its biological functions. Int. J. Mol. Sci. 15, 6356–6377 (2014).
doi: 10.3390/ijms15046356
Yu, Y. J. et al. Therapeutic bispecific antibodies cross the blood-brain barrier in nonhuman primates. Sci. Transl. Med. 6, 261ra154 (2014).
doi: 10.1126/scitranslmed.3009835
Bien-Ly, N. et al. Transferrin receptor (TfR) trafficking determines brain uptake of TfR antibody affinity variants. J. Exp. Med. 211, 233–244 (2014).
doi: 10.1084/jem.20131660
Niewoehner, J. et al. Increased brain penetration and potency of a therapeutic antibody using a monovalent molecular shuttle. Neuron 81, 49–60 (2014).
doi: 10.1016/j.neuron.2013.10.061
Sade, H. et al. A human blood-brain barrier transcytosis assay reveals antibody transcytosis influenced by pH-dependent receptor binding. PLoS ONE 9, e96340 (2014).
doi: 10.1371/journal.pone.0096340
Pulgar, V. M. Transcytosis to cross the blood brain barrier, new advancements and challenges. Front. Neurosci. 12, 1019 (2019).
doi: 10.3389/fnins.2018.01019
Kanekura, T., Miyauchi, T., Tashiro, M. & Muramatsu, T. Basigin, a new member of the immunoglobulin superfamily: genes in different mammalian species, glycosylation changes in the molecule from adult organs and possible variation in the N-terminal sequences. Cell Struct. Funct. 16, 23–30 (1991).
doi: 10.1247/csf.16.23
Yoshida, S. et al. Homo-oligomer formation by basigin, an immunoglobulin superfamily member, via its N-terminal immunoglobulin domain. Eur. J. Biochem. 267, 4372–4380 (2000).
doi: 10.1046/j.1432-1327.2000.01482.x
Cui, H.-Y. et al. Dimerization is essential for HAb18G/CD147 promoting tumor invasion via MAPK pathway. Biochem. Biophys. Res. Commun. 419, 517–522 (2012).
doi: 10.1016/j.bbrc.2012.02.049
Koch, C. et al. T cell activation-associated epitopes of CD147 in regulation of the T cell response, and their definition by antibody affinity and antigen density. Int. Immunol. 11, 777–786 (1999).
doi: 10.1093/intimm/11.5.777
Weksler, B., Romero, I. A. & Couraud, P.-O. The hCMEC/D3 cell line as a model of the human blood brain barrier. Fluids Barriers CNS 10, 16 (2013).
doi: 10.1186/2045-8118-10-16
Helms, H. C. et al. In vitro models of the blood–brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use. J. Cereb. Blood Flow Metab. 36, 862–890 (2016).
doi: 10.1177/0271678X16630991
Nielsen, S. S. E. et al. Improved method for the establishment of an in vitro blood-brain barrier model based on porcine brain endothelial cells. J. Vis. Exp. https://doi.org/10.3791/56277 (2017).
doi: 10.3791/56277
pubmed: 28994773
pmcid: 5752332
Zheng, Y. et al. Minipig as a potential translatable model for monoclonal antibody pharmacokinetics after intravenous and subcutaneous administration. MAbs 4, 243–255 (2012).
doi: 10.4161/mabs.4.2.19387
Carroll, R. C. et al. Dynamin-dependent endocytosis of ionotropic glutamate receptors. Proc. Natl. Acad. Sci. USA 96, 14112–14117 (1999).
doi: 10.1073/pnas.96.24.14112
Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).
doi: 10.1038/nmeth.2019