A5019640668- Monoclonal and Polyclonal Antibodies Research
- Neonatal Respiratory Health Research
- Blood groups and transfusion
- Respiratory Support and Mechanisms
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- Immunodeficiency and Autoimmune Disorders
- Glycosylation and Glycoproteins Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cardiac Ischemia and Reperfusion
- Cholesterol and Lipid Metabolism
- Asthma and respiratory diseases
- Alzheimer's disease research and treatments
- Lipoproteins and Cardiovascular Health
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- IL-33, ST2, and ILC Pathways
- Platelet Disorders and Treatments
- Inflammation biomarkers and pathways
- Cytokine Signaling Pathways and Interactions
- Genetic Associations and Epidemiology
GlaxoSmithKline (United Kingdom)
2008-2018
Molecular Discovery (United Kingdom)
2008-2017
Age UK
2014-2015
Background Tumour necrosis factor alpha (TNF-α) is a pleiotropic cytokine with both injurious and protective functions, which are thought to diverge at the level of its two cell surface receptors, TNFR1 TNFR2. In setting acute injury, selective inhibition predicted attenuate death inflammation associated TNF-α, while sparing or potentiating effects TNFR2 signalling. We developed potent antagonist (GSK1995057) using novel domain antibody (dAb) therapeutic assessed efficacy in vitro, vivo...
Asthma is a multifactorial disease, in which the intricate interplay between genetic and environmental factors underlies overall phenotype of disease. Using genome-wide scan for linkage population comprising Danish families, we identified novel linked locus on chromosome 1qter (LOD 3.6, asthma) supporting evidence this was both asthma atopic-asthma phenotypes GAIN (Genetics International Network) families. The putative susceptibility gene progressively localized to 4.5 Mb region 1q adjacent...
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 high levels novel, pre-existing human anti-VH (HAVH) autoantibody. In the presence HAVH autoantibodies, GSK1995057 induced vitro due to binding autoantibodies framework region dAb. The epitope on was characterized and dAbs reduced generated; pharmacological comparability determined in-vitro systems...
Background: Tumor necrosis factor-α (TNF) is strongly implicated in the development of acute respiratory distress syndrome (ARDS), but its potential as a therapeutic target has been hampered by complex biology. TNF signals through two receptors, p55 and p75, which play differential roles pulmonary edema formation during ARDS. We have recently shown that inhibition novel domain antibody (dAb™) attenuated ventilator-induced lung injury. In current study we explored efficacy this mouse models...
<h3></h3> Neutrophil recruitment into the bronchoalveolar space is central to pathogenesis of acute respiratory distress syndrome injury (ARDS), and occurs via interaction with lung microvascular endothelium. Tumour Necrosis Factor (TNF) a key mediator in these processes, activating endothelial cells inducing changes permeability, as well priming neutrophils (a pre-requisite for neutrophil-mediated tissue damage) modulating neutrophil lifespan. TNF signals through two cell surface receptors,...
<h3></h3> Alveolar epithelial activation and disruption of the alveolar barrier promote recruitment neutrophils into space cause oedema respectively thereby playing key roles in pathogenesis Acute Respiratory Distress Syndrome (ARDS). Tumour necrosis factor alpha (TNF) is an early mediator inflammation ARDS. TNF signals through two cell surface receptors, TNFR1 TNFR2 initiating distinct signalling pathways cellular responses. Using a novel, highly selective domain antibody (dAb™), dummy dAb...