ArticleBioengineered bugs
Biologic TNFα-inhibitors that cross the human blood-brain barrier.
Article in Bioengineered bugs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Adverse events of tumor necrosis factor alpha inhibitors for the treatment of ankylosing spondylitis: A meta-analysis of randomized, placebo-controlled trials.Frontiers in pharmacology · 2023Pooled it
- Role of Glutamate Excitotoxicity in Glioblastoma Growth and Its Implications in Treatment.Cell biology international · 2025Review
- Exosomal TNF-α mediates voltage-gated Na+ channel 1.6 overexpression and contributes to brain tumor-induced neuronal hyperexcitability.The Journal of clinical investigation · 2024Article
- Corticosteroid-free adalimumab-cyclophosphamide combination therapy for acute phase neuro-Behçet's disease: a case report.Journal of rheumatic diseases · 2024Article
- 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
- Blood-Brain Barrier Disruption and Its Involvement in Neurodevelopmental and Neurodegenerative Disorders.International journal of molecular sciences · 2022Review
- Biomarker of Neuroinflammation in Parkinson's Disease.International journal of molecular sciences · 2022Review
- Article
- Central Nervous System Delivery of Antibodies and Their Single-Domain Antibodies and Variable Fragment Derivatives with Focus on Intranasal Nose to Brain Administration.Antibodies (Basel, Switzerland) · 2021Review
- Hippocampal TNF-α Signaling Mediates Heroin Withdrawal-Enhanced Fear Learning and Withdrawal-Induced Weight Loss.Molecular neurobiology · 2021Article
- Anti-TNF-α Compounds as a Treatment for Depression.Molecules (Basel, Switzerland) · 2021Review
- Treatment with TNF-α inhibitors versus methotrexate and the association with dementia and Alzheimer's disease.Alzheimer's & dementia (New York, N. Y.) · 2021Article
- Dendritic cells in tumor microenvironment promoted the neuropathic pain via paracrine inflammatory and growth factors.Bioengineered · 2020Article
- Blood-Brain Barrier and Delivery of Protein and Gene Therapeutics to Brain.Frontiers in aging neuroscience · 2019Article
- Tumor necrosis factor α Inhibition for Alzheimer's Disease.Journal of central nervous system disease · 2017Review
- CXCR3 promotes plaque formation and behavioral deficits in an Alzheimer's disease model.The Journal of clinical investigation · 2015Article
- Challenges and opportunities in absorption, distribution, metabolism, and excretion studies of therapeutic biologics.The AAPS journal · 2012Review
- Discovering context-specific relationships from biological literature by using multi-level context terms.BMC medical informatics and decision making · 2012Article
- Brain-penetrating tumor necrosis factor decoy receptor in the mouse.Drug metabolism and disposition: the biological fate of chemicals · 2011Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor (TNF)α inhibitors (TNFI) are a major class of biologic therapeutics, and include decoy receptor and monoclonal antibody (MAb) therapeutics that block TNFα action. TNFα is a pro-inflammatory cytokine in brain disease, such as stroke, brain or spinal cord injury, or Alzheimer disease. However, the biologic TNFIs cannot be developed for the brain, because these large molecules do not cross the blood-brain barrier (BBB). Brain penetrating forms of TNFα decoy receptors or anti-TNFα antibody therapeutics can be re-engineered as IgG fusion proteins with a BBB molecular Trojan horse, such as the mAb against the human insulin receptor (HIR). The HIRMAb undergoes receptor-mediated transport across the BBB via the endogenous insulin receptor, and carries into brain the fused biologic TNFI. A fusion protein of the HIRMAb and the type II TNF receptor (TNFR) extracellular domain, designated the HIRMAb-TNFR fusion protein, has been engineered and expressed in stably transfected Chinese hamster ovary (CHO) cells. The HIRMAb-TNFR fusion protein binds both the HIR and TNFα with low nM affinity. The HIRMAb cross reacts with the Rhesus monkey insulin receptor, and the HIRMAb-TNFR is rapidly, and selectively, taken up by primate brain at concentrations that inhibit TNFα. In addition, a fusion protein of the HIRMAb and a therapeutic single chain Fv (ScFv) antibody has been engineered and also expressed in stably transfected CHO cells. The BBB molecular Trojan horse platform technology allows for the engineering of brain-penetrating recombinant proteins as new biologic therapeutics for the human 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.