A5076631069- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- vaccines and immunoinformatics approaches
- Immune Response and Inflammation
- Cancer Immunotherapy and Biomarkers
- Virus-based gene therapy research
- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Influenza Virus Research Studies
- Hepatitis B Virus Studies
- Renal cell carcinoma treatment
- Respiratory viral infections research
- Hepatitis C virus research
- Pneumonia and Respiratory Infections
- Pancreatic function and diabetes
- Cancer-related Molecular Pathways
- RNA Interference and Gene Delivery
- interferon and immune responses
- Poxvirus research and outbreaks
- Bone Metabolism and Diseases
- Xenotransplantation and immune response
Guy's Hospital
2015-2021
King's College London
2011-2021
London Cancer
2020-2021
University College London
1997-2021
Medical Research Council
2015-2020
Cancer Research UK
2020
CRUK Lung Cancer Centre of Excellence
2020
Kings Health Partners
2015-2020
Helmholtz Centre for Infection Research
2005-2014
W. L. Gore & Associates (Germany)
2013
Significance The design of effective T-cell vaccines against pathogens and tumor antigens is challenged by the highly inefficient identification subset peptides from a given antigen that effectively stimulate an immune response. Here we report relative hydrophobicity receptor contact residues markedly enriched in immunogenic major histocompatibility complex class I epitopes both human murine MHCs, self pathogen-derived epitopes. Incorporating into epitope prediction models increases...
ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates clinical T receptor (TCR) analysis reveals significantly higher number expanded TCR...
Stabilization of virus protein structure and nucleic acid integrity is challenging yet essential to preserve the transcriptional competence live recombinant viral vaccine vectors in absence a cold chain. When coupled with needle-free skin delivery, such platform would address an unmet need global coverage against HIV other pathogens. Herein, we show that simple dissolvable microneedle array (MA) delivery system preserves immunogenicity vaccines encoded by human adenovirus type 5 (rAdHu5)....
Immunosuppressive drugs in clinical transplantation are necessary to inhibit the immune response donor antigens. Although they effective controlling acute rejection, do not prevent long-term transplant loss from chronic rejection. In addition, immunosuppressive have adverse side effects, including increased rate of infections and malignancies. Adoptive cell therapy with human Tregs represents a promising strategy for induction tolerance. Phase I/II trials transplanted patients already...
A novel subset of human regulatory B-cells has recently been described. They arise from within the transitional B-cell subpopulation and are characterised by production IL-10. appear to be significant importance in regulating T-cell immunity vivo. Despite this important function, molecular mechanisms which they control activation incompletely defined. Here we show that produced more IL-10 expressed higher levels receptor after CD40 engagement compared other subsets. Furthermore, under...
Programmed cell death protein 1 (PD-1) is expressed on T cells upon receptor (TCR) stimulation. PD-1 ligand (PD-L1) in most tumor environments, and its binding to drives them apoptosis or into a regulatory phenotype. The fact that PD-L1 itself also activation has been largely neglected. Here, we demonstrate ligation human CD25-depleted CD4 + cells, combined with CD3/TCR stimulation, induces their conversion highly suppressive cells. Furthermore, this effect was prominent memory (CD45RA −...
ABSTRACT To stimulate both local and systemic immune responses against Trypanosoma cruzi , Salmonella enterica serovar Typhimurium aroA was exploited as a DNA delivery system for cruzipain (SCz). In murine model we compared SCz alone (GI) or coadministered with carrying plasmid encoding granulocyte-macrophage colony-stimulating factor (GII), well protocols in which priming followed by boosting recombinant (rCz) admixed either CpG-ODN (GIII) MALP-2, synthetic derivative of...
Cytokine immunotherapies targeting T lymphocytes are attractive clinical interventions against viruses and tumors. In the mouse, homeostasis of memory α/β CD8 + cells natural killer (NK) is significantly improved with increased IL-15 bioavailability. contrast, role “transpresented” on human T-cell development in vivo unknown. We found that both CD4 immune system (HIS) mice highly sensitive to transpresented vivo, naïve (CD62L CD45RA ) phenotype − CD45RO subsets being following “boosting.”...
Background Passive transfer of antibodies not only provides immediate short-term protection against disease, but also can be exploited as a therapeutic tool. However, the 'humanization' murine monoclonal (mAbs) is time-consuming and expensive process that has inherent drawback potentially altering antigenic specificity and/or affinity. The immortalization human B cells represents an alternative for obtaining mAbs, relies on availability biological samples from vaccinated individuals or...
The superoxide-generating enzyme Nox2 contributes to hypertension and cardiovascular remodeling triggered by activation of the renin-angiotensin system. Multiple Nox2-expressing cells are implicated in angiotensin II-induced (Ang II-induced) pathophysiology, but importance leukocyte subsets is poorly understood. Here, we investigated role T cells, particularly Tregs. Mice globally deficient displayed increased numbers Tregs heart at baseline, whereas Ang effector cell (Teff) infiltration was...
Abstract The macrophage-activating lipopeptide-2 (MALP-2) is an agonist of the TLR heterodimer 2/6, which exhibits potent activity as mucosal adjuvant, promoting strong humoral and cellular responses. Although B cells expressing TLR2/6 are potential targets, very little known about effect MALP-2 on cells. Studies were performed using total spleen or purified from WT mice animals deficient in TLR2, T cells, specific subpopulations They demonstrated that promotes a cell-independent activation...
There is an increasing body of evidence suggesting that the transfer preformed MHC class I:peptide complexes between a virus-infected cell and uninfected APC, termed cross-dressing, represents important mechanism Ag presentation to CD8+ T cells in host defense. However, although it has been shown memory can be activated by dendritic (DCs) cross-dressed from parenchymal cells, unknown whether conditions exist during virus infection which naive are primed differentiate cytolytic effectors...
Numerical and functional defects in plasmacytoid dendritic cells (pDCs) are an important hallmark of progressive HIV-1 infection, yet its etiology remains obscure. p17 matrix protein (p17) modulates a variety cellular responses, biological activity depends on the expression receptors (p17Rs) surface target cells. In this study, we show that peripheral blood pDCs express p17Rs their freshly isolated sensitive to stimulation. Upon treatment, undergo phenotypic differentiation with...
Abstract B cells have been reported to promote graft rejection through alloantibody production. However, there is growing evidence that can contribute the maintenance of tolerance. Here, we used a mouse model MHC-class I mismatched skin transplantation investigate contribution survival. We demonstrate adoptive transfer prolongs survival but only when were isolated from mice housed in low sterility “conventional” (CV) facilities and not pathogen free (SPF). prolongation was lost IL-10...
The generation of tissue resident memory (TRM) cells at the body surfaces to provide a front line defence against invading pathogens represents an important goal in vaccine development for wide variety pathogens. It has been widely assumed that local delivery mucosae is necessary achieve aim. Here we characterise novel micro-needle array (MA) system fabricated deliver live recombinant human adenovirus type 5 vector (AdHu5) encoding HIV-1 gag. We demonstrate rapid dissolution kinetics...