Trial reportJournal of clinical immunology2013
Autoantibodies to variable heavy (VH) chain Ig sequences in humans impact the safety and clinical pharmacology of a VH domain antibody antagonist of TNF-α receptor 1.
Trial report in Journal of clinical immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 75 citations in OpenAlex.
- Tisagenlecleucel immunogenicity in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma.Blood advances · 2021Trial
- Trial
- Specificity of human anti-variable heavy (VH ) chain autoantibodies and impact on the design and clinical testing of a VH domain antibody antagonist of tumour necrosis factor-α receptor 1.Clinical and experimental immunology · 2015Trial
- The Promise of Single-Domain Antibodies as Ocular Therapeutics: A Narrative Review.International journal of molecular sciences · 2026Review
- Immunogenicity risk assessment for tailored mitigation and monitoring of biotherapeutics during development: recommendations from the European Immunogenicity Platform.Frontiers in immunology · 2025Review
- Immunogenicity risk assessment and mitigation for engineered antibody and protein therapeutics.Nature reviews. Drug discovery · 2024Review
- Specific imaging of CD8 + T-Cell dynamics with a nanobody radiotracer against human CD8β.European journal of nuclear medicine and molecular imaging · 2024Article
- Nanobodies: From High-Throughput Identification to Therapeutic Development.Molecular & cellular proteomics : MCP · 2024Review
- Single-Domain Antibodies-Novel Tools to Study and Treat Allergies.International journal of molecular sciences · 2024Review
- Single-domain antibodies and aptamers drive new opportunities for neurodegenerative disease research.Frontiers in immunology · 2024Review
- TNF and TNF receptors as therapeutic targets for rheumatic diseases and beyond.Nature reviews. Rheumatology · 2023Review
- NANOBODYInternational journal of molecular sciences · 2023Review
- Potential Promises and Perils of Human Biological Treatments for Immunotherapy in Veterinary Oncology.Veterinary sciences · 2023Review
- A bispecific T cell engager recruits both type 1 NKT and Vγ9Vδ2-T cells for the treatment of CD1d-expressing hematological malignancies.Cell reports. Medicine · 2023Article
- Understanding Retinal Vasculitis Associated with Brolucizumab: Complex Pathophysiology or Occam's Razor?Ocular immunology and inflammation · 2022Article
- Immunogenicity assessment of bispecific antibody-based immunotherapy in oncology.Journal for immunotherapy of cancer · 2022Review
- Aggregates Associated with Instability of Antibodies during Aerosolization Induce Adverse Immunological Effects.Pharmaceutics · 2022Article
- A Small Virus to Deliver Small Antibodies: New Targeted Therapies Based on AAV Delivery of Nanobodies.Microorganisms · 2021Review
- Brolucizumab-related retinal vasculitis: emerging disconnect between clinical trials and real world.Eye (London, England) · 2021Article
- Immunogenicity Risk Profile of Nanobodies.Frontiers in immunology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo investigate the impact of a new class of anti-Ig autoantibodies reactive with variable heavy (VH) chain framework sequences (human anti-VH autoantibodies) on the pharmacology and safety of an anti-TNFR1 VH domain antibody (GSK1995057) in healthy human subjects.
methodsSingle-blind, randomised, placebo-controlled dose escalation study in which healthy males (n = 28) received a single GSK1995057 intravenous infusion of 0.0004, 0.002 and 0.01 mg/kg. All enrolled subjects were pre-screened for human anti-VH (HAVH) autoantibody status and prospectively stratified accordingly. Serum samples from drug-naïve, HAVH-positive volunteers were used to investigate the effect of HAVH/GSK1995057 complexes on the activation of TNFR1 and cytokine release in vitro.
resultsHuman anti-VH autoantibodies were detected in approximately 50 % of drug-naïve healthy human subjects and clinical and in vitro studies were performed to evaluate their impact on the pharmacology and safety of GSK1995057. We demonstrated that formation of HAVH autoantibody/GSK1995057 complexes activated TNFR1 and caused cytokine release in vitro in some, but not all, of the human cell types tested. When GSK1995057 was administered to healthy subjects, clinical and physiological signs of cytokine release were observed in two HAVH autoantibody-positive subjects following GSK1995057 infusion. In vitro, HAVH autoantibody levels correlated with TNFR1-dependent cytokine release and propensity for cytokine release in humans following GSK1995057 dosing.
conclusionsOur data support a greater focus on the impact of pre-existing, drug-reactive autoantibodies on the development of antibody fragments and biotherapeutics targeting cell surface receptors.
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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.