Trial reportClinical and experimental immunology2015
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.
Trial report in Clinical and experimental immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 41 citations in OpenAlex.
- A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study.European journal of anaesthesiology · 2020Trial
- The Promise of Single-Domain Antibodies as Ocular Therapeutics: A Narrative Review.International journal of molecular sciences · 2026Review
- Rethinking immunogenicity: an integrated approach reveals the PK/PD impact of pre-existing and drug-sustaining ADA.Bioanalysis · 2026Article
- Article
- Article
- Rapid and Wash-Free Anti-Drug Antibody Assay Enabled by a Complementary Nanoluciferase Biosensor.Analytical chemistry · 2025Article
- A synthetic heavy chain variable domain antibody library (VHL) provides highly functional antibodies with favorable developability.Protein science : a publication of the Protein Society · 2025Article
- Exploring TNFR1: from discovery to targeted therapy development.Journal of translational medicine · 2025Review
- Immunogenicity risk assessment and mitigation for engineered antibody and protein therapeutics.Nature reviews. Drug discovery · 2024Review
- Preclinical assessment of a novel human antibody VH domain targeting mesothelin as an antibody-drug conjugate.Molecular therapy oncolytics · 2023Article
- TNF and TNF receptors as therapeutic targets for rheumatic diseases and beyond.Nature reviews. Rheumatology · 2023Review
- A structure-based engineering approach to abrogate pre-existing antibody binding to biotherapeutics.PloS one · 2021Article
- Pulmonary Delivery of Biological Drugs.Pharmaceutics · 2020Review
- Selective Targeting of TNF Receptors as a Novel Therapeutic Approach.Frontiers in cell and developmental biology · 2020Review
- David vs. Goliath: The Structure, Function, and Clinical Prospects of Antibody Fragments.Antibodies (Basel, Switzerland) · 2019Review
- Selection of Single-Domain Antibodies towards Western Equine Encephalitis Virus.Antibodies (Basel, Switzerland) · 2018Article
- A New Venue of TNF Targeting.International journal of molecular sciences · 2018Review
- Molecular characterization of human anti-hinge antibodies derived from single-cell cloning of normal human B cells.The Journal of biological chemistry · 2018Article
- Ribosome display for the rapid generation of high-affinity Zika-neutralizing single-chain antibodies.PloS one · 2018Article
- Inhibition of TNF Receptor p55 By a Domain Antibody Attenuates the Initial Phase of Acid-Induced Lung Injury in Mice.Frontiers in immunology · 2017Article
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 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During clinical trials of a tumour necrosis factor (TNF)-R1 domain antibody (dAb™) antagonist (GSK1995057), infusion reactions consistent with cytokine release were observed in healthy subjects with high levels of a novel, pre-existing human anti-VH (HAVH) autoantibody. In the presence of HAVH autoantibodies, GSK1995057 induced cytokine release in vitro due to binding of HAVH autoantibodies to a framework region of the dAb. The epitope on GSK1995057 was characterized and dAbs with reduced binding to HAVH autoantibodies were generated; pharmacological comparability was determined in human in-vitro systems and in-vivo animal experiments. A Phase I clinical trial was conducted to investigate the safety and tolerability of the modified dAb (GSK2862277). A significant reduction in HAVH binding was achieved by adding a single alanine residue at the C-terminus to create GSK2862277. Screening a pool of healthy donors demonstrated a reduced frequency of pre-existing autoantibodies from 51% to 7%; in all other respects, GSK2862277 and the parent dAb were comparable. In the Phase I trial, GSK2862277 was well tolerated by both the inhaled and intravenous routes. One subject experienced a mild infusion reaction with cytokine release following intravenous dosing. Subsequently, this subject was found to have high levels of a novel pre-existing antibody specific to the extended C-terminus of GSK2862277. Despite the reduced binding of GSK2862277 to pre-existing HAVH autoantibodies, adverse effects associated with the presence of a novel pre-existing antibody response specific to the modified dAb framework were identified and highlight the challenge of developing biological antagonists to this class of receptor.
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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.