ArticleMolecular therapy. Methods & clinical development2020
Tetravalent Bispecific Tandem Antibodies Improve Brain Exposure and Efficacy in an Amyloid Transgenic Mouse Model.
Article in Molecular therapy. Methods & clinical development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Antibody-Based Biologics for CNS Disorders.Antibodies (Basel, Switzerland) · 2026Review
- Brain Delivery of Antibody-Derived Biologicals for Alzheimer's Disease: An Updated Narrative Review.Antibodies (Basel, Switzerland) · 2026Review
- Bispecific brain-penetrant antibodies for treatment of Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Review
- High-affinity transferrin receptor binding improves brain delivery of bispecific antibodies at tracer dose.Fluids and barriers of the CNS · 2025Article
- The blood-brain barrier: a help and a hindrance.Brain : a journal of neurology · 2025Review
- The effects of dose, valency, and affinity on TfR-mediated brain delivery in vivo.Fluids and barriers of the CNS · 2025Article
- Comparative Radiotracing Quantifies Brain Cellular Uptake and Catabolism of Bispecific Antibodies Targeting Transferrin Receptor and CD98hc.ACS chemical neuroscience · 2025Article
- Increasing brain half-life of antibodies by additional binding to myelin oligodendrocyte glycoprotein, a CNS specific protein.Fluids and barriers of the CNS · 2025Article
- Bispecific antibody shuttles targeting CD98hc mediate efficient and long-lived brain delivery of IgGs.Cell chemical biology · 2024Article
- Design and engineering of bispecific antibodies: insights and practical considerations.Frontiers in bioengineering and biotechnology · 2024Review
- Receptor-mediated drug delivery of bispecific therapeutic antibodies through the blood-brain barrier.Frontiers in drug delivery · 2023Article
- Grabody B, an IGF1 receptor-based shuttle, mediates efficient delivery of biologics across the blood-brain barrier.Cell reports methods · 2022Article
- A Historical Review of Brain Drug Delivery.Pharmaceutics · 2022Review
- Kinetics of Blood-Brain Barrier Transport of Monoclonal Antibodies Targeting the Insulin Receptor and the Transferrin Receptor.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Current and Emerging Strategies for Enhancing Antibody Delivery to the Brain.Pharmaceutics · 2021Review
- Mathematical Models of Blood-Brain Barrier Transport of Monoclonal Antibodies Targeting the Transferrin Receptor and the Insulin Receptor.Pharmaceuticals (Basel, Switzerland) · 2021Article
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Authors and funding
26 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most antibodies display very low brain exposure due to the blood-brain barrier (BBB) preventing their entry into brain parenchyma. Transferrin receptor (TfR) has been used previously to ferry antibodies to the brain by using different formats of bispecific constructs. Tetravalent bispecific tandem immunoglobulin Gs (IgGs) (TBTIs) containing two paratopes for both TfR and protofibrillar forms of amyloid-beta (Aβ) peptide were constructed and shown to display higher brain penetration than the parent anti-Aβ antibody. Additional structure-based mutations on the TfR paratopes further increased brain exposure, with maximal enhancement up to 13-fold in wild-type mice and an additional 4-5-fold in transgenic (Tg) mice harboring amyloid plaques, the main target of our amyloid antibody. Parenchymal target engagement of extracellular amyloid plaques was demonstrated using
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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.