ArticleJournal of biotechnology2010
Selective targeting of a TNFR decoy receptor pharmaceutical to the primate brain as a receptor-specific IgG fusion protein.
Article in Journal of biotechnology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 120 citations in OpenAlex.
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- Brain Delivery of Antibody-Derived Biologicals for Alzheimer's Disease: An Updated Narrative Review.Antibodies (Basel, Switzerland) · 2026Review
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- Remyelination as a therapeutic target in the treatment of multiple sclerosis.AIMS neuroscience · 2025Review
- Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer's disease mice.Journal of translational medicine · 2024Article
- Receptor-mediated transcytosis for brain delivery of therapeutics: receptor classes and criteria.Frontiers in drug delivery · 2024Review
- Cyanidin prevents MDPV withdrawal-induced anxiety-like effects and dysregulation of cytokine systems in rats.Brain research · 2023Article
- Treatment of Parkinson's disease with biologics that penetrate the blood-brain barrier via receptor-mediated transport.Frontiers in aging neuroscience · 2023Review
- Current Update on Transcellular Brain Drug Delivery.Pharmaceutics · 2022Review
- Efficacy and Safety of a Brain-Penetrant Biologic TNF-α Inhibitor in Aged APP/PS1 Mice.Pharmaceutics · 2022Article
- Engineering antibody and protein therapeutics to cross the blood-brain barrier.Antibody therapeutics · 2022Review
- Elevated TNF-α Leads to Neural Circuit Instability in the Absence of Interferon Regulatory Factor 8.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Phytochemicals as inhibitors of tumor necrosis factor alpha and neuroinflammatory responses in neurodegenerative diseases.Neural regeneration research · 2022Review
- 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
- Crossing the Blood-Brain Barrier: Advances in Nanoparticle Technology for Drug Delivery in Neuro-Oncology.International journal of molecular sciences · 2022Review
- Biologic TNF-α inhibitors reduce microgliosis, neuronal loss, and tau phosphorylation in a transgenic mouse model of tauopathy.Journal of neuroinflammation · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Decoy receptors, such as the human tumor necrosis factor receptor (TNFR), are potential new therapies for brain disorders. However, decoy receptors are large molecule drugs that are not transported across the blood-brain barrier (BBB). To enable BBB transport of a TNFR decoy receptor, the human TNFR-II extracellular domain was re-engineered as a fusion protein with a chimeric monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb acts as a molecular Trojan horse to ferry the TNFR therapeutic decoy receptor across the BBB. The HIRMAb-TNFR fusion protein was expressed in stably transfected CHO cells, and was analyzed with electrophoresis, Western blotting, size exclusion chromatography, and binding assays for the HIR and TNFalpha. The HIRMAb-TNFR fusion protein was radio-labeled by trititation, in parallel with the radio-iodination of recombinant TNFR:Fc fusion protein, and the proteins were co-injected in the adult Rhesus monkey. The TNFR:Fc fusion protein did not cross the primate BBB in vivo, but the uptake of the HIRMAb-TNFR fusion protein was high and 3% of the injected dose was taken up by the primate brain. The TNFR was selectively targeted to brain, relative to peripheral organs, following fusion to the HIRMAb. This study demonstrates that decoy receptors may be re-engineered as IgG fusion proteins with a BBB molecular Trojan horse that selectively targets the brain, and enables penetration of the BBB in vivo. IgG-decoy receptor fusion proteins represent a new class of human neurotherapeutics.
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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.