ArticlePloS one2022
An innovative strategy to identify new targets for delivering antibodies to the brain has led to the exploration of the integrin family.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 6 citations in OpenAlex.
- Nanoscopic analysis of tight junction organization in in vitro blood-brain barrier models.Fluids and barriers of the CNS · 2026Article
- Artificial Intelligence-Driven Strategies for Targeted Delivery and Enhanced Stability of RNA-Based Lipid Nanoparticle Cancer Vaccines.Pharmaceutics · 2025Review
- Identifying molecular tags selectively retained on the surface of brain endothelial cells to generate artificial targets for therapy delivery.Fluids and barriers of the CNS · 2023Article
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Authors and funding
10 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundIncreasing brain exposure of biotherapeutics is key to success in central nervous system disease drug discovery. Accessing the brain parenchyma is especially difficult for large polar molecules such as biotherapeutics and antibodies because of the blood-brain barrier. We investigated a new immunization strategy to identify novel receptors mediating transcytosis across the blood-brain barrier.
methodWe immunized mice with primary non-human primate brain microvascular endothelial cells to obtain antibodies. These antibodies were screened for their capacity to bind and to be internalized by primary non-human primate brain microvascular endothelial cells and Human Cerebral Microvascular Endothelial Cell clone D3. They were further evaluated for their transcytosis capabilities in three in vitro blood-brain barrier models. In parallel, their targets were identified by two different methods and their pattern of binding to human tissue was investigated using immunohistochemistry.
results12 antibodies with unique sequence and internalization capacities were selected amongst more than six hundred. Aside from one antibody targeting Activated Leukocyte Cell Adhesion Molecule and one targeting Striatin3, most of the other antibodies recognized β1 integrin and its heterodimers. The antibody with the best transcytosis capabilities in all blood-brain barrier in vitro models and with the best binding capacity was an anti-αnβ1 integrin. In comparison, commercial anti-integrin antibodies performed poorly in transcytosis assays, emphasizing the originality of the antibodies derived here. Immunohistochemistry studies showed specific vascular staining on human and non-human primate tissues.
conclusionsThis transcytotic behavior has not previously been reported for anti-integrin antibodies. Further studies should be undertaken to validate this new mechanism in vivo and to evaluate its potential in brain delivery.
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