A5026700573- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- Leprosy Research and Treatment
- Cancer Cells and Metastasis
- Pharmacological Effects of Natural Compounds
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer Research and Treatments
- Biosimilars and Bioanalytical Methods
- Immune Response and Inflammation
- vaccines and immunoinformatics approaches
- Glycosylation and Glycoproteins Research
- Cancer Genomics and Diagnostics
- Parasitic Infections and Diagnostics
- Advanced Breast Cancer Therapies
- Hepatitis B Virus Studies
- Single-cell and spatial transcriptomics
- Chemokine receptors and signaling
- Liver Disease Diagnosis and Treatment
GlaxoSmithKline (United States)
2013-2024
GlaxoSmithKline (United Kingdom)
2010-2023
Age UK
2009-2022
Molecular Oncology (United States)
2009
GlaxoSmithKline (India)
2002
Wellcome Trust
1992-1997
Hammersmith Hospital
1988-1994
Royal Victoria Hospital
1988-1991
University of Ulster
1988-1991
National Cancer Institute
1988-1989
Mouse syngeneic tumor models are widely used tools to demonstrate activity of novel anti-cancer immunotherapies. Despite their widespread use, a comprehensive view tumor-immune compositions and relevance human tumors has only begun emerge. We propose each model possesses unique infiltrate profile that can be probed with immunotherapies inform on anti-tumor mechanisms treatment strategies in similar profiles. In support this endeavor, we characterized the microenvironment four commonly they...
Abstract Hyperexpression of the programmed death 1 (PD-1) molecule is a hallmark exhausted T-cells, having negative impact on T-cell activation and function. We studied longitudinally 18 hepatitis B e antigen (HBeAg)–positive patients undergoing treatment with direct antivirals (telbivudine or lamivudine) to determine relationship between treatment-induced viremia reduction HBeAg seroconversion respect PD-1 levels reactivity. expression was assessed by (1) flow cytometry (2) quantitative...
Two lines of evidence in the current study indicate that antigen processing is a major factor, addition to MHC binding and T cell repertoire, determines Ir gene responsiveness epitope immunodominance. First, immunization with synthetic peptides myoglobin sequences revealed new reactivities had not appeared after priming native myoglobin. For example, B10.S mice (H-2S) immune equine predominantly responded peptide 102-118, whereas there was little, if any, response this B10.BR (H-2k)...
The CAMPATH-1 (CD52) antigen is a 21-28 kDa glycopeptide which highly expressed on lymphocytes and macrophages coupled to the membrane by glycosylphosphatidylinositol (GPI) anchoring structure. function of this molecule unknown. However, it an extremely good target for complement-mediated attack antibody-mediated cellular cytotoxicity. humanized CAMPATH-1H antibody, directed against CD52, very efficient at mediating lymphocyte depletion in vivo, currently being used clinical trials lymphoid...
<h3>Introduction</h3> OX-40 co-stimulatory signaling plays a role in mounting anti-tumor immune responses and clinical trials targeting this pathway are ongoing. However, the association of with protein expression outcomes pathological features non-small cell lung cancer (NSCLC) largely unknown. <h3>Methods</h3> Surgically-resected stage I-III NSCLC specimens (<i>N</i> = 100) were stained by immunohistochemistry (IHC) for following markers: OX-40, PD-L1, PD-1, CD3, CD4, CD8, CD45RO, CD57,...
Abstract Following uptake by macrophages, live mycobacteria initially reside within an immature phagosome that resists acidification and retains access to recycling endosomes. Glycolipids are exported from the mycobacterial become available for immune recognition CD1-restricted T cells. The aim of this study was explore possibility lipoproteins might similarly escape act as targets in cells infected with mycobacteria. We have focused on a 19-kDa lipoprotein Mycobacterium tuberculosis...
Patients with severe rheumatoid arthritis who had failed treatment conventional therapies were treated a course of five or 10 daily intravenous infusions CAMPATH‐1H, humanized antibody against the CD52 antigen, resulting in profound depletion peripheral blood mononuclear cells. During subsequent 18 months, lymphocytes analysed for sub‐populations by fluorescence‐activated cell sorter (FACS) and proliferation response to polyclonal T‐cell stimulation anti‐CD3 staphylococcal enterotoxin B...
Oncostatin M (OSM) has been implicated in the pathophysiology of rheumatoid arthritis (RA) through its effect on inflammation and joint damage. GSK315234 is a humanised anti-OSM Immunoglobulin G1 (IgG1) monoclonal antibody (mAb). This 3-part study examines safety, tolerability efficacy patients with active RA.This was (Parts A, B C), multicenter study. Part A were randomised, double-blind, placebo-controlled, Bayesian adaptive dose finding studies to investigate tolerability, efficacy,...
GSK3050002, a humanized IgG1κ antibody with high binding affinity to human CCL20, was administered in first-in-human study evaluate safety, pharmacokinetics (PK) and pharmacodynamics (PD). An experimental skin suction blister model employed assess target engagement the ability of compound inhibit recruitment inflammatory CCR6 expressing cells.This randomized, double-blind (sponsor open), placebo-controlled, single-centre, single ascending intravenous dose escalation trial 48 healthy male...
Interleukin (IL)-7 signalling modulates T cell activity and is implicated in numerous autoimmune diseases. The present study investigated the safety, pharmacokinetics, target engagement, pharmacodynamics immunogenicity of GSK2618960, an IL-7 receptor-α subunit (CD127) monoclonal antibody.A double-blind (sponsor-unblind) a single intravenous infusion either GSK2618960 (0.6 mg kg-1 or 2.0 ) placebo was carried out 18 healthy subjects over 24 weeks.GSK2618960 well tolerated; there were no...
Abstract Murine macrophages produce nitric oxide (NO) from L‐arginine on stimulation with lipopolysaccharide (LPS), alone or interferon‐γ (IFN‐γ). The effect of incubation low concentrations LPS NO synthesis subsequent was investigated, using a murine macrophage cell line, J774, and peritoneal CBA mice. Cells which had been incubated produced significantly lower amounts NO, expressed levels synthase activity, following IFN‐γ LPS, high concentration LPS. This not reversed by tumor necrosis...
Summary Expression of the lymph node homing and CC‐chemokine receptor 7 (CCR7), with L‐selectin (CD62L), has been shown to divide human memory T cells into two functionally distinct subsets. We generated a polyclonal antibody against murine CCR7 used this study expression on T‐cell Using flow cytometric staining for visualisation in association CD62L CD44, major population CD4 or CD8 expressing were found be high CD44 low , which would suggest naïve cell phenotype. By analogy studies, could...
In recent years, there has been considerable interest in mAb-based induction of costimulatory receptor signaling as an approach to combat cancer. However, promising nonclinical data have yet translate a meaningful clinical benefit. Inducible T-cell costimulator (ICOS) is important for immune responses. Using novel clinical-stage anti-ICOS immunoglobulin G4 mAb (feladilimab), which induces but does not deplete ICOS+ T cells and their rodent analogs, we provide end-to-end evaluation the...
Potent immunological adjuvants are urgently required to complement recombinant and synthetic vaccines. However, it has not been possible derive new principles for the design of vaccine from knowledge mechanism immunogenicity. Carbonyl-amino condensations, which essential inductive interaction between antigen-presenting cells T helper cells, were tested as a target enhancement immune responses. Enzymic oxidation cell-surface galactose increase aminereactive carbonyl groups on murine...
Activated T cells drive a range of immune‐mediated inflammatory diseases. LAG‐3 is transiently expressed on recently activated CD4 + and CD8 cells. We describe the engineering first‐in‐human clinical study (NCT02195349) GSK2831781 (an afucosylated humanized IgG1 monoclonal antibody enhanced with high affinity for Fc receptors antibody‐dependent cellular cytotoxicity capabilities), which depletes expressing was tested in phase I/Ib, double‐blind, placebo‐controlled study, randomized 40...
Fifteen overlapping synthetic peptides, spanning the entire amino acid sequence of Mycobacterium tuberculosis 19-kDa protein, were used to identify epitopes recognized by murine T cells. Five 15 peptides tested able elicit in vitro lymph node cell proliferative responses C57BL/10 mice primed footpad inoculation with homologous peptide. Analysis congenic strains revealed H-2 restriction response four peptides. However, one peptide, 19.7 (residues 61 80), induced all haplotypes tested. This...
Abstract The 65‐kDa stress protein from Mycobacterium bovis (Bacillus Calmette Guérin) elicited T cell proliferation and antibody responses in seven B10 congenic mouse strains with different H‐2 haplotypes. To analyze determinants on this antigen, peptides corresponding to six predicted epitopes, one defined B epitope were synthesized. Mice either immunized the whole antigen specificity of response was ascertained respect peptides, or mice tested for proliferative molecule. results showed...