- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Rheumatoid Arthritis Research and Therapies
- Heat shock proteins research
- Toxin Mechanisms and Immunotoxins
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immune responses and vaccinations
- Endoplasmic Reticulum Stress and Disease
- Cystic Fibrosis Research Advances
- Systemic Lupus Erythematosus Research
- Glycosylation and Glycoproteins Research
- Pharmacological Effects of Natural Compounds
- Immune Response and Inflammation
- HIV Research and Treatment
- Respiratory viral infections research
- Neonatal Respiratory Health Research
- vaccines and immunoinformatics approaches
- Receptor Mechanisms and Signaling
- Innovative Microfluidic and Catalytic Techniques Innovation
- Hepatitis B Virus Studies
- Antimicrobial Peptides and Activities
- Ion channel regulation and function
Roivant Sciences (United States)
2024
St George's, University of London
2013-2024
Institute For Cancer Vaccine & Immunotherapy
2023
Davidson College
2020
Southampton General Hospital
2019
University of North Dakota
2014
King's College London
2003-2011
Guy's Hospital
2000-2006
University at Buffalo, State University of New York
1985-2005
King's College School
2005
Abstract Objective To explore the changes in serologic variables and clinical disease activity following B lymphocyte depletion 22 patients with rheumatoid arthritis (RA). Methods was attained using combination therapy based on monoclonal anti‐CD20 antibody rituximab. Levels of a indicator inflammation, C‐reactive protein (CRP), antimicrobial antibodies, autoantibodies including IgA‐, IgM‐, IgG‐class factors (RF), antibodies to cyclic citrullinated peptide (anti‐CCP) were assayed. Results...
Abstract Rheumatoid arthritis (RA) is the most common, crippling human autoimmune disease. Using Western blotting and tandem mass spectroscopy, we have identified endoplasmic reticulum chaperone BiP, a 78-kDa glucose-regulated protein, as possible autoantigen. It preferentially stimulated increased proliferation of synovial T cells from patients with RA but not other arthritides. Mice established collagen- or pristane-induced developed IgG Abs to BiP. Although BiP injected in CFA failed...
We characterized the effect of insulin on collagen synthesis in 21-day-old fetal rat calvaria maintained organ culture. All experiments were done presence 100 mg/dl glucose and 3 mM phosphate, which found to be optimal concentrations for responsiveness. tested (1 nM 1 microM) increased percentage being synthesized central bone, whereas only high hormone (100 periosteum. Insulin at labeling type I but did not alter or III Proinsulin was approximately 10-100 times less effective than...
Background Patients with metastatic skin disease in malignant melanoma can be difficult to treat effectively, often requiring repeated treatments different modalities an attempt control their disease. Treatment of nonsurgically resectable deposits is unsatisfactory, as they are multiple and recurring. Anecdotal evidence from individual use imiquimod superficial metastases intralesional interleukin (IL)-2 subcutaneous suggests that the combination may more effective bulky Objectives To...
Summary Immune checkpoint inhibitors (ICIs) have achieved huge clinical success. However, many still limited response rates, and are prohibitively costly. There is a need for effective affordable ICIs, as well local manufacturing capacity to improve accessibility, especially low‐to‐middle income countries (LMICs). Here, we successfully expressed three key ICIs (anti‐PD‐1 Nivolumab, anti‐NKG2A Monalizumab, anti‐LAG‐3 Relatimab) transiently in Nicotiana benthamiana tabacum plants. The were...
Abstract Objective The stress protein and endoplasmic reticulum chaperone, immunoglobulin binding (BiP), is an autoantigen in rheumatoid arthritis (RA). Stress proteins, however, may have extracellular functions, mediated via cell surface receptors, that include immunomodulatory functions. We sought to determine whether cell‐free BiP present the synovial fluid (SF) of patients with RA further investigate possible antiinflammatory properties peripheral blood mononuclear cells (PBMCs) vitro....
Abstract Objective Following the demonstration that stress protein, BiP, prevented induction of collagen‐induced arthritis (CIA) in HLA–DRB*0101 +/+ (HLA–DR1 ) mice, we investigated immunotherapeutic ability BiP to suppress disease during active phase CIA HLA–DR1 and DBA/1 mice. Methods was administered either subcutaneously or intravenously DBA/1, , interleukin‐4 (IL‐4)–knockout mice at onset arthritis. Immune cells were used adoptive transfer studies restimulated culture with type II...
The tuberculosis vaccine, Bacille Calmette-Guerin (BCG), also affords protection against non-tuberculous diseases attributable to heterologous immune mechanisms such as trained innate immunity, activation of non-conventional T-cells, and cross-reactive adaptive immunity. Aerosol vaccine delivery can target responses toward the primary site infection for a respiratory pathogen. Therefore, we hypothesised that aerosol BCG would enhance cross-protective action severe acute syndrome...
Cystic fibrosis (CF) is caused by mutations in the gene encoding CF transmembrane conductance regulator (CFTR) protein. Although affects multiple organs, lung disease main cause of morbidity and mortality, therapy expected to provide a mutation-agnostic option for treatment. SP-101 recombinant adeno-associated virus (AAV) vector carrying human
Attenuated and heat-killed mycobacteria display demonstrable activity against cancer in the clinic; however, induced immune response is poorly characterised potential biomarkers of ill-defined. We investigated whether three mycobacterial preparations currently used clinic (BCG Mycobacterium vaccae obuense) can stimulate anti-tumour effector responses human γδ T-cells. T-cell were by measuring cytokine production, expression granzyme B cytotoxicity tumour target cells. Results show that...
Cystic fibrosis (CF) is a serious genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Approved small molecule therapies benefit majority of people with (pwCF), but unfortunately not all. Gene addition offers mutation agnostic treatment option for all pwCF. SP-101 an adeno-associated virus gene therapy vector (AAV2.5T) that has been optimized efficient human airway cell transduction, and contains functional regulated shortened CFTR minigene (
We have examined the frequencies of Tγδ cells in blood, synovial fluids, and membranes patients with rheumatoid arthritis (RA) blood from age‐matched controls Immunocyto‐chemical immunohistochemical techniques were used monoclonal antibodies BB3 A13 to define a major minor subset respectively. Together, these identify majority (if not all) peripheral cells. Significantly lower levels found RA compared controls, whilst higher but significant numbers fluids or paired samples Scattered only...
Patients with metastatic skin disease in malignant melanoma are difficult to treat, unresectable lesions proving the biggest challenge. We have recently published data showing a significant clinical response patients multiple in-transit metastases treated combination of topical imiquimod and intralesional interleukin (IL)-2. Here we report results immunological analysis aim highlighting correlations our findings.To investigate systemic effects localized treatment accessible melanoma,...
The human stress protein BiP (immunoglobulin binding protein) has been implicated in the pathogenesis of rheumatoid arthritis (RA) since was found to stimulate synovial T-cell proliferation and anti-BiP antibodies are present serum RA patients. aim this study development a rapid reproducible enzyme-linked immunosorbent assay (ELISA) determine specificity sensitivity RA.An ELISA developed that detected BiP. prevalence determined sera from patients with early established RA, antedating onset...
Objectives. We have reported that synovial fluid T cells from patients with rheumatoid arthritis (RA) proliferate in response to the endoplasmic reticulum molecular chaperone immunoglobulin binding protein (BiP). The aim of present work was clone and define responding this protein.
Abstract Objective Colorectal cancer is immunogenic. However, it also associated with suppression of host immunity. Identifying the mechanisms involved in immune necessary to develop future immunotherapeutic strategies. The aim this study was assess cell function colorectal patients. Method A total 80 patients (41 male) prior treatment and 38 matched controls (21 were recruited. Venous blood samples taken. White composition determined using monoclonal antibodies. Levels cytokines IFN‐γ,...
Acetate supplementation reduces neuroglia activation and pro-inflammatory cytokine expression in rat models of neuroinflammation Lyme neuroborreliosis. Because single-dose glyceryl triacetate (GTA) treatment increases brain phosphocreatine AMP levels, we postulate that GTA modulates adenosine metabolizing enzymes receptors, which may be a possible mechanism to reduce neuroinflammation. To test this hypothesis, quantified the ability alter levels ecto-5'-nucleotidase (CD73), kinase (AK), A2A...
The dosing interval for effective recombinant adeno-associated virus (rAAV)-mediated gene therapy of cystic fibrosis lung disease remains unknown. Here, we assessed the durability rAAV2.5T-fCFTRΔR-mediated transgene expression and neutralizing antibody (NAb) responses in lungs adult wild-type ferrets. Within first 3 months following rAAV2.5T-fCFTRΔR delivery to lung,