A5051502902- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- T-cell and B-cell Immunology
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Receptor Mechanisms and Signaling
- Immune cells in cancer
- CAR-T cell therapy research
- MicroRNA in disease regulation
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Cancer Cells and Metastasis
- RNA Interference and Gene Delivery
- Hematopoietic Stem Cell Transplantation
- Chemical Synthesis and Analysis
- Computational Drug Discovery Methods
- HER2/EGFR in Cancer Research
- Biotechnology and Related Fields
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Cell Image Analysis Techniques
- Health Literacy and Information Accessibility
- Ion channel regulation and function
Sheffield Hallam University
2018-2022
AstraZeneca (United Kingdom)
2021
Babraham Institute
2012-2019
Luton and Dunstable Hospital
2013-2016
Data Harbor (United States)
2015
GlaxoSmithKline (United Kingdom)
2008
Murine syngeneic tumor models are critical to novel immuno-based therapy development, but the molecular and immunologic features of these still not clearly defined. The translational relevance differences between is fully understood, impeding appropriate preclinical model selection for target validation, ultimately hindering drug development. Across a panel commonly used murine models, we showed variable responsiveness immunotherapies. We array comparative genomic hybridization, whole-exome...
Pathogenic mycobacteria, including Mycobacterium tuberculosis and bovis, cause significant morbidity mortality worldwide. However, the vaccine strain bovis BCG, unlike virulent strains, triggers extensive apoptosis of infected macrophages, a step necessary for elicitation robust protective immunity. We here demonstrate that M. BCG Toll-like receptor 2 (TLR2)-dependent microRNA-155 (miR-155) expression, which involves signaling cross talk among phosphatidylinositol 3-kinase (PI3K), protein...
A single microRNA (miRNA) can regulate the expression of many genes, though level repression imparted on any given target is generally low. How then selective pressure for a miRNA/target interaction maintained across long evolutionary distances? We addressed this problem by disrupting in vivo between miR-155 and PU.1 mice. Remarkably, proved to be key promoting optimal T cell–dependent B cell responses, previously unrecognized role PU.1. Mechanistically, inhibits expression, leading Pax5...
The 5-HT(3) receptor is a member of the 'Cys-loop' family ligand-gated ion channels that mediate fast excitatory and inhibitory transmission in nervous system. Current evidence points towards native receptors originating from homomeric assemblies 5-HT(3A) or heteromeric assembly 5-HT(3B). Novel genes encoding 5-HT(3C), 5-HT(3D), 5-HT(3E) have recently been described but functional importance these proteins unknown. In present study, silico analysis (confirmed by partial cloning) indicated...
// Geoffrey S. Williams 1 , Bina Mistry Sandrine Guillard Jane Coates Ulrichsen Alan M. Sandercock Jun Wang 2 Andrea González-Muñoz Julie Parmentier 3 Chelsea Black 4 Jo Soden 5 Jim Freeth Jelena Jovanović Rebecca Leyland Rafia Al-Lamki Andrew J. Leishman Steven Rust Ross Stewart Lutz Jermutus John R. Bradley Vahe Bedian Viia Valge-Archer Ralph Minter Robert W. Wilkinson MedImmune Ltd., Granta Park, Cambridge, CB21 6GH, UK Department of Medicine, University Addenbrooke’s...
Purpose: To generate and characterize a murine GITR ligand fusion protein (mGITRL-FP) designed to maximize valency the potential agonize receptor for cancer immunotherapy.Experimental Design: The EC50 value of mGITRL-FP was compared with an anti-GITR antibody in vitro agonistic cell-based reporter assay. We assessed impact dose, schedule, Fc isotype on antitumor activity T-cell modulation CT26 tumor model. OX40L-FP targeting OX40, B16F10-Luc2 models. Combination antibodies PD-L1, PD-1, or...
The production of high-affinity antibodies by B cells is essential for pathogen clearance. Antibody affinity antigen increased through the maturation in germinal centers (GCs). This an iterative process which cycle between proliferation coupled with acquisition mutations and antigen-based positive selection, resulting retention highest-affinity cell clones. posttranscriptional regulator microRNA-155 (miR-155) critical efficient maintenance GCs; however, cellular molecular mechanism miR-155...
A fast antibody response can be critical to contain rapidly dividing pathogens. This achieved by the expansion of antigen-specific B cells in T-cell help followed differentiation into plasmablasts. MicroRNA-155 (miR-155) is required for optimal T-cell-dependent extrafollicular responses via regulation PU.1, although cellular processes underlying this defect are largely unknown. Here, we show that miR-155 regulates early B-blasts and later on survival proliferation plasmablasts a...
A recombinant Newcastle Disease Virus (NDV), encoding either a human (NDVhuGM-CSF, MEDI5395) or murine (NDVmuGM-CSF) GM-CSF transgene, combined broad oncolytic activity with the ability to significantly modulate genes related immune functionality in tumor cells. Replication lines was diminished relative Nonetheless, intratumoral injection of NDVmuGM-CSF conferred antitumor effects three syngeneic models vivo; efficacy further augmented by concomitant treatment anti-PD-1/PD-L1 T-cell...
Background Lab Tests Online-UK celebrated its 10th anniversary in 2014 and to mark the occasion first comprehensive survey of website users was undertaken. Methods A pop-up box with a link Survey Monkey used offer chance participate survey, which live from 4 March 11 April 2014. Results Six hundred sixty-one participants started questionnaire 338 completed all demographic questions. Although is designed aimed at patients public, significant number respondents were health-care professionals...
Abstract Glucocorticoid-induced TNFR-related protein (GITR) is a member of the tumor necrosis factor receptor (TNFR) superfamily. GITR expressed constitutively on regulatory T cells (Tregs) and up-regulated other following activation. Agonistic antibodies to have demonstrated significant activity in preclinical models cancer. Here we describe generation characterisation ligand (GITRL) fusion (FP) (MEDI1873), currently phase 1 clinical trials. Protein engineering was used generate series...
Abstract Programmed death-ligand 1 (PD-L1) expression is a survival mechanism employed by tumours to mediate immune evasion and tumour progression. PD-1/PD-L1-targeted therapies have revolutionised the cancer therapy landscape due their ability promote durable anti-tumour responses in select patients with advanced cancers. However, some are unresponsive, hyper-progressive or develop resistance. Better characterisation of 3D architecture solid utilising cell culture could provide an...
Meeting abstracts GITR is a member of the TNFR superfamily proteins and expressed on resting regulatory T cells other cells, NK following activation. Signals through have been shown to drive increased cell activity reduced function. In order
Abstract The pre-clinical assessment of immuno-oncology (IO) therapies can be enabled by the use murine syngeneic tumors established in immuno-competent mice. With aims selecting relevant models and minimizing animal experimentation reducing number tested, full characterisation at transcriptomic genomic level is a key objective for scientists. Model includes global aCGH, exon array analysis FACS profiling alongside exome sequencing. model data undergoing hypothesis free driven analyses which...
Abstract GITR is a member of the TNFR superfamily proteins and expressed on resting regulatory T-cells other following activation. Signals through have been shown to drive increased T-cell activity reduced function. In order explore potential therapeutically targeting in cancer setting, we generated mouse GITRL fusion protein (mGITRL FP) consisting extracellular domain mGITRL linked structural an IgG Fc domain. The antitumor pharmacodynamic effects this molecule were then explored colorectal...
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