ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2020
Antibody screening using a human iPSC-based blood-brain barrier model identifies antibodies that accumulate in the CNS.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Strategies to Screen and Evaluate Brain Targeting Antibodies Using an iPSC-Derived Blood-Brain Barrier Model.Antibodies (Basel, Switzerland) · 2025Article
- Identification of Variable Lymphocyte Receptors That Target the Human Blood-Brain Barrier.Pharmaceutics · 2025Article
- Development of a Novel Immunoprecipitation Method for Extracting Monoclonal Antibodies From Brain Tissue and Its Application to Assessing In Vivo Brain Penetration in Mouse via Liquid Chromatography-Mass Spectrometry.Biomedical chromatography : BMC · 2025Article
- Peripheral Inflammation and Insulin Resistance: Their Impact on Blood-Brain Barrier Integrity and Glia Activation in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Device-assisted strategies for drug delivery across the blood-brain barrier to treat glioblastoma.Communications materials · 2025Review
- Review
- A Pralidoxime Nanocomplex Formulation Targeting Transferrin Receptors for Reactivation of Brain Acetylcholinesterase After Exposure of Mice to an Anticholinesterase Organophosphate.International journal of nanomedicine · 2024Article
- Subcellular trafficking and transcytosis efficacy of different receptor types for therapeutic antibody delivery at the blood‒brain barrier.Fluids and barriers of the CNS · 2023Article
- Enhanced in vivo blood brain barrier transcytosis of macromolecular cargo using an engineered pH-sensitive mouse transferrin receptor binding nanobody.Fluids and barriers of the CNS · 2023Article
- EnhancedbioRxiv : the preprint server for biology · 2023Article
- Modelling a Human Blood-Brain Barrier Co-Culture Using an Ultrathin Silicon Nitride Membrane-Based Microfluidic Device.International journal of molecular sciences · 2023Article
- The 46.1 Antibody Mediates Neurotensin Uptake into the CNS and the Effects Depend on the Route of Intravenous Administration.Pharmaceutics · 2022Article
- Identification of lamprey variable lymphocyte receptors that target the brain vasculature.Scientific reports · 2022Article
- Article
- Integrating in vitro disease models of the neurovascular unit into discovery and development of neurotherapeutics.Current opinion in biomedical engineering · 2021Article
- Brain Barriers and brain fluids research in 2020 and the fluids and barriers of the CNS thematic series on advances in in vitro modeling of the blood-brain barrier and neurovascular unit.Fluids and barriers of the CNS · 2021Article
- Recent progress and new challenges in modeling of human pluripotent stem cell-derived blood-brain barrier.Theranostics · 2021Review
- Relationship Between Amyloid-β Deposition and Blood-Brain Barrier Dysfunction in Alzheimer's Disease.Frontiers in cellular neuroscience · 2021Review
- Commentary on human pluripotent stem cell-based blood-brain barrier models.Fluids and barriers of the CNS · 2020Article
- Strategies to identify, engineer, and validate antibodies targeting blood-brain barrier receptor-mediated transcytosis systems for CNS drug delivery.Expert opinion on drug deliveryReview
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Drug delivery across the blood-brain barrier (BBB) remains a significant obstacle for the development of neurological disease therapies. The low penetration of blood-borne therapeutics into the brain can oftentimes be attributed to the restrictive nature of the brain microvascular endothelial cells (BMECs) that comprise the BBB. One strategy beginning to be successfully leveraged is the use of endogenous receptor-mediated transcytosis (RMT) systems as a means to shuttle a targeted therapeutic into the brain. Limitations of known RMT targets and their cognate targeting reagents include brain specificity, brain uptake levels, and off-target effects, driving the search for new and potentially improved brain targeting reagent-RMT pairs. To this end, we deployed human-induced pluripotent stem cell (iPSC)-derived BMEC-like cells as a model BBB substrate on which to mine for new RMT-targeting antibody pairs. A nonimmune, human single-chain variable fragment (scFv) phage display library was screened for binding, internalization, and transcytosis across iPSC-derived BMECs. Lead candidates exhibited binding and internalization into BMECs as well as binding to both human and mouse BBB in brain tissue sections. Antibodies targeted the murine BBB after intravenous administration with one particular clone, 46.1-scFv, exhibiting a 26-fold increase in brain accumulation (8.1 nM). Moreover, clone 46.1-scFv was found to associate with postvascular, parenchymal cells, indicating its successful receptor-mediated transport across the BBB. Such a new BBB targeting ligand could enhance the transport of therapeutic molecules into the brain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.