A5068519558- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Asthma and respiratory diseases
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Pediatric health and respiratory diseases
- Immune cells in cancer
- CAR-T cell therapy research
- Biochemical and Molecular Research
- Advanced Breast Cancer Therapies
- NF-κB Signaling Pathways
- Rheumatoid Arthritis Research and Therapies
- Cancer-related Molecular Pathways
- Cytokine Signaling Pathways and Interactions
- Respiratory viral infections research
- Respiratory and Cough-Related Research
- Ferroptosis and cancer prognosis
- Lung Cancer Research Studies
- Viral gastroenteritis research and epidemiology
- Liver Diseases and Immunity
- Diabetes and associated disorders
- Adenosine and Purinergic Signaling
Quorn (United Kingdom)
2025
AstraZeneca (United Kingdom)
2005-2019
University College Dublin
2018
Imperial College London
2018
Edinburgh Cancer Research
2018
Loughborough University
2005-2013
University of Oxford
2011
Weatherford College
2010
Roslin Cells (United Kingdom)
2003
La Jolla Institute for Immunology
2001-2002
<h3>Background</h3> Immune checkpoint blockade (ICB) promotes adaptive immunity and tumor regression in some cancer patients. However, patients with immunologically “cold” tumors, tumor-resident innate immune cell activation may be required to prime an response so exploit the full potential of ICB. Whilst Toll-like receptor (TLR) agonists have been used topically successfully treat superficial skin systemic TLR not well-tolerated. <h3>Methods</h3> The human cells TLR7 8 agonism was measured...
The thymus leukemia antigen (TL) is a nonclassical class I molecule, expressed abundantly on intestinal epithelial cells. We show that, in contrast to other major histocompatibility complex (MHC) molecules that bind CD8αβ, TL preferentially binds the homotypic form of CD8α (CD8αα). Thus, tetramers react specifically CD8αα-expressing cells, including most intraepithelial lymphocytes. Compared with which recognizes same MHC as T cell receptor (TCR) and thus acts TCR coreceptor, high-affinity...
Abstract The relative ability of Th1 and Th2 T cells to help B remains controversial as do the mechanisms by which both cell subsets provide in vivo. Whether this affects clonal expansion and/or differentiation has been difficult assess due low frequency Ag-specific lymphocytes. We have employed a novel technique directly monitor lymphocytes OVA-specific TCR transgenic were polarized toward or phenotype vitro. These then transferred into syngeneic recipients, along with receptor hen egg...
A defect in RelB, a member of the Rel/nuclear factor (NF)-κB family transcription factors, affects antigen presenting cells and formation lymphoid organs, but its role T lymphocyte differentiation is not well characterized. Here, we show that RelB deficiency mice leads to selective decrease NKT cells. must be expressed an irradiation-resistant host cell can CD1d negative, indicating expressing does contribute directly positive selection CD1d-dependent Like RelB-deficient mice, aly/aly with...
Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations asthma chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of 100 identified serotypes, ∼90% bind domain 1 human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development therapies; however, ICAM-1 is also required host defence regulation cell trafficking,...
// 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...
CpG-containing immunostimulatory DNA sequences (ISS), which signal through TLR9, are being developed as a therapy for allergic indications and have proven to be safe well tolerated in humans when administrated via the pulmonary route. In contrast, ISS inhalation has unexplained toxicity rodents, express TLR9 monocyte/macrophage lineage cells plasmacytoid DCs (pDCs) B cells, principal TLR9-expressing humans. We therefore investigated mechanisms underlying this rodent-specific its implications...
Monocyte-derived dendritic cells (moDC) have been widely used in cancer immunotherapy but show significant donor-to-donor variability and low capacity for the cross-presentation of tumour-associated antigens (TAA) to CD8+ T cells, greatly limiting success this approach. Given recent developments induced pluripotency relative ease with which pluripotent stem (iPS) cell lines may be generated from individuals, we succeeded differentiating (DC) human leukocyte antigen (HLA)-A*0201+ iPS (iPS...
Abstract Background:CB307 is a tri-specific variable heavy-chain antibody fragment against PSMA, CD137, and human serum albumin. It designed to mitigate hepatotoxicity by activating T cells only in the PSMA-positive tumors increase drug half-life albumin binding. This Phase I study investigated safety tolerability of CB307 as monotherapy or with pembrolizumab.Methods: Patients who were heavily pretreated solid enrolled dose-escalation phase monotherapy. Additional efficacy assessed expansion...
Abstract CT7439 is a small molecule kinase inhibitor of cyclin-dependent kinases CDK12/CDK13 that received FDA IND approval in 2023. In addition to inhibiting CDK12/13, acts as monovalent glue degrader cyclin K (CCNK), the required for CDK12/13 function. Proteomics quantification by DIA LCS/LCSMS mass spectrometry was conducted after exposure 30 nM at 4 & 24 hr. OV-90 cells were cultured media and exposed various concentrations time points. Combination studies with PARP inhibitors...
Summary Asthma is a heterogeneous disease that has been increasing in incidence throughout western societies and cytokines, including proinflammatory tumour necrosis factor alpha (TNF-α), have implicated the pathogenesis of asthma. Anti-TNF-α therapies established successfully clinic for diseases such as rheumatoid arthritis Crohn's disease. TNF-α-blocking strategies are now being trialled asthma; however, their mode action poorly understood. Based on observation TNF-α induces lymph node...
BACKGROUND AND PURPOSE Toll-like receptor 7 (TLR7) agonists have potential in the treatment of allergic diseases. However, therapeutic utility current low molecular weight TLR7 is limited by their systemic activity, resulting unwanted side effects. We developed a series TLR7-selective 'antedrugs', including SM-324405 and AZ12441970, which contain an ester group rapidly cleaved plasma to reduce exposure. EXPERIMENTAL APPROACH Agonist activity at parent acid metabolite was assessed vitro...
The relative roles of innate immunity and antigen-specific T cells in rheumatoid arthritis remain controversial. Previous studies demonstrated that T-helper type 1 irrelevant antigen specificity (ovalbumin) induced a transient BALB/c mice, which recapitulates many the pre-articular articular features human disease is associated with emergence autoreactive B-cell responses to joint-specific antigens. However, mechanisms underlying this phenomenon were unclear.The aim study was dissect...
Topical TLR7 agonists such as imiquimod are highly effective for the treatment of dermatological malignancies; however, their efficacy in nondermatological tumors has been less successful. We report that oral administration novel TLR7-selective small molecule agonist; SM-276001, leads to induction an inflammatory cytokine and chemokine milieu activation a diverse population immune effector cells including T B lymphocytes, NK NKT cells. Oral SM-276001 IFNα, TNFα IL-12p40 reduction tumor...
TLR7 agonists modulate Th2 immune responses through mechanisms that have not been fully elucidated. Suppression of IL-5 production from Ag- or phytohemagglutinin-stimulated human PBMCs by the antedrug AZ12441970 was mediated via type I IFN-dependent and IFN-independent activation plasmacytoid dendritic cells, B monocytes. The inhibition T cell-derived IFN-α acting directly on activated cells. IL-10 shown to be involved in mechanism required cell-cell interaction. Notch signaling implicated...
Triggering innate immune responses through TLRs is expected to be a novel therapeutic strategy for the treatment of allergic diseases. TLR agonists are able modulate Th2 undefined mechanisms. We investigated mechanism action suppression with antedrug TLR7 agonist. The rapidly metabolized by plasma esterases an acid reduced activity limit systemic responses. Topical administration this compound inhibited features airway inflammatory response in rat and murine airways model. Type I IFN played...
Abstract There is considerable evidence that regulatory cytokines play an important role in mediating the systemic tolerance found after oral administration of protein Ags. Although most existing work has focused on such as IL-4, IL-10, and TGF-β, recent from TCR transgenic systems suggests induction accompanied by priming Ag-specific IFN-γ production. also been implicated a mediator T cell other models vivo vitro, including induced aerosol protein. We show here feeding tolerogenic doses OVA...
It is widely accepted that allergic asthma orchestrated by T helper type 2 lymphocytes specific for inhaled allergen. However, it remains unclear where and when cell activation division occurs after allergen challenge, whether these factors have a significant impact on airways inflammation. We therefore employed CD4-T receptor transgenic adoptive transfer model in conjunction with laser scanning cytometry to characterize the location timing of vivo. Thus, first time we directly assessed...