ArticleMolecular pharmaceutics2010
Pharmacokinetics and brain uptake of a genetically engineered bifunctional fusion antibody targeting the mouse transferrin receptor.
Article in Molecular pharmaceutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 120 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
- Serotransferrin enhances transferrin receptor-mediated brain uptake of antibodies.Drug delivery and translational research · 2025Article
- Adeno-associated viruses escort nanomaterials to specific cells and tissues.bioRxiv : the preprint server for biology · 2025Article
- Skeleton keys and Trojan horses: a review of therapeutic delivery to the brain.Frontiers in cell and developmental biology · 2025Review
- Chemotherapy in pediatric brain tumor and the challenge of the blood-brain barrier.Cancer medicine · 2023Review
- Age, dose, and binding to TfR on blood cells influence brain delivery of a TfR-transported antibody.Fluids and barriers of the CNS · 2023Article
- Receptor-mediated drug delivery of bispecific therapeutic antibodies through the blood-brain barrier.Frontiers in drug delivery · 2023Article
- Small molecule inhibitor of tau self-association in a mouse model of tauopathy: A preventive study in P301L tau JNPL3 mice.PloS one · 2023Article
- ImmunoPET imaging of amyloid-beta in a rat model of Alzheimer's disease with a bispecific, brain-penetrating fusion protein.Translational neurodegeneration · 2022Article
- Efficacy and Safety of a Brain-Penetrant Biologic TNF-α Inhibitor in Aged APP/PS1 Mice.Pharmaceutics · 2022Article
- Recent advances in drug delivery and targeting to the brain.Journal of controlled release : official journal of the Controlled Release Society · 2022Review
- A Brain-Targeting Bispecific-Multivalent Antibody Clears Soluble Amyloid-Beta Aggregates in Alzheimer's Disease Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- IgG Fusion Proteins for Brain Delivery of Biologics via Blood-Brain Barrier Receptor-Mediated Transport.Pharmaceutics · 2022Review
- A Historical Review of Brain Drug Delivery.Pharmaceutics · 2022Review
- Dual-targeted magnetic mesoporous silica nanoparticles reduce brain amyloid-β burden via depolymerization and intestinal metabolism.Theranostics · 2022Article
- Review of Advanced Drug Trials Focusing on the Reduction of Brain Beta-Amyloid to Prevent and Treat Dementia.Journal of experimental pharmacology · 2022Review
- Neural stem cells secreting bispecific T cell engager to induce selective antiglioma activity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- pH-responsive antibodies for therapeutic applications.Journal of biomedical science · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Monoclonal antibodies (MAbs) are potential new therapeutics for brain diseases. However, MAbs do not cross the blood-brain barrier (BBB). The present work describes the genetic engineering of a fusion protein composed of a therapeutic single chain Fv (ScFv) antibody and a mouse/rat chimeric MAb against the mouse transferrin receptor (TfR). The TfRMAb acts as a molecular Trojan horse to ferry the therapeutic ScFv across the BBB in vivo in the mouse. The ScFv is fused to the carboxyl terminus of the heavy chain of the chimeric TfRMAb, and this fusion protein is designated cTfRMAb-ScFv. Chinese hamster ovary cells were permanently transfected, and a high secreting cell line in serum free medium was cloned. The cTfRMAb-ScFv fusion protein was purified to homogeneity on gels and Western blotting with protein G affinity chromatography. The cTfRMAb-ScFv fusion protein was bifunctional and bound both the target antigen, as determined by ELISA, and the mouse TfR, as determined with a radio-receptor assay. The cTfRMAb-ScFv fusion protein was radio-iodinated with the Bolton-Hunter reagent, and a pharmacokinetics study in mice showed that the fusion protein was rapidly cleared from blood with a median residence time of 175 +/- 32 min. The fusion protein was avidly taken up by brain with a % injected dose (ID)/g of 3.5 +/- 0.7, as compared to an MAb with no receptor specificity, which was 0.06 +/- 0.01% ID/g. These studies demonstrate that therapeutic MAbs may be re-engineered as fusion proteins with BBB molecular Trojan horses for targeted delivery across the BBB in vivo.
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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.