A5040801002- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Viral-associated cancers and disorders
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Polyomavirus and related diseases
- Melanoma and MAPK Pathways
- Colorectal Cancer Treatments and Studies
- Cytomegalovirus and herpesvirus research
- Cutaneous Melanoma Detection and Management
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- Parvovirus B19 Infection Studies
- Lymphoma Diagnosis and Treatment
- vaccines and immunoinformatics approaches
- Neutropenia and Cancer Infections
- Full-Duplex Wireless Communications
- Glioma Diagnosis and Treatment
- Brain Metastases and Treatment
- Antenna Design and Analysis
- Cancer Treatment and Pharmacology
- Cancer Genomics and Diagnostics
- Respiratory viral infections research
- Herpesvirus Infections and Treatments
University of Birmingham
2015-2025
University Hospitals Birmingham NHS Foundation Trust
2007-2024
Queen Elizabeth Hospital Birmingham
2012-2024
NIHR Surgical Reconstruction and Microbiology Research Centre
2018-2024
Queen Elizabeth Hospital
2023
Cancer Research UK Clinical Trials Unit
2003-2022
Queen Elizabeth Hospital
2022
Heartlands Hospital
2003-2021
Bristol-Myers Squibb (United States)
2017
NIHR CRUK Experimental Cancer Medicine Centre
2015
Primary infection with virus can stimulate a vigorous cytotoxic T cell response. The magnitude of the antigen-specific component versus bystander primary response remains controversial. In this study, we have used tetrameric major histocompatibility complex–peptide complexes to directly visualize cluster differentration (CD)8+ cells during immune Epstein-Barr (EBV) in humans. We show that massive expansion activated, occurs virus. one individual, specific for single EBV epitope comprised 44%...
Abstract Purpose: To conduct a phase I clinical trial with second-generation oncolytic herpes simplex virus (HSV) expressing granulocyte macrophage colony-stimulating factor (Onco VEXGM-CSF) to determine the safety profile of virus, look for evidence biological activity, and identify dosing schedule later studies. Experimental Design: The was administered by intratumoral injection in patients cutaneous or s.c. deposits breast, head neck gastrointestinal cancers, malignant melanoma who had...
Epstein-Barr virus (EBV) can display different forms of latent infection in B-cell lines vitro; however, the types normally established by vivo remain largely unexplored. Here we have approached this question analyzing viral RNAs present mononuclear cells freshly isolated from blood 14 infectious mononucleosis patients undergoing primary EBV and 6 long-term carriers. Reverse transcription-PCR amplifications were carried out with a panel oligonucleotide primers probes which specifically...
The role of prophylactic antibacterial agents after chemotherapy remains controversial.We conducted a randomized, double-blind, placebo-controlled trial in patients who were receiving cyclic for solid tumors or lymphoma and at risk temporary, severe neutropenia (fewer than 500 neutrophils per cubic millimeter). Patients randomly assigned to receive either mg levofloxacin once daily matching placebo seven days during the expected neutropenic period. primary outcome was incidence clinically...
Tebentafusp is a first-in-class bispecific fusion protein designed to target gp100 (a melanoma-associated antigen) through high affinity T-cell receptor (TCR) binding domain and an anti-CD3 engaging domain, which redirects T cells kill gp100-expressing tumor cells. Here, we report multicenter phase I/II trial of tebentafusp in metastatic melanoma (NCT01211262) focusing on the mechanism action tebentafusp.
Epstein-Barr virus (EBV), a human gamma-herpesvirus, can establish both nonproductive (latent) and productive (lytic) infections. Although the CD8+ cytotoxic T lymphocyte (CTL) response to latently infected cells is well characterized, very little known about cell controls over lytic infection; this imbalance in our understanding belies importance of virus-replicative lesions several aspects EBV disease pathogenesis. The present work shows that primary CTL infectious mononucleosis patients...
This is a phase II clinical trial investigating the safety and efficacy of intravenous vaccination with mature autologous dendritic cells (DCs) pulsed ex vivo liver tumor cell line lysate (HepG2) in patients advanced hepatocellular carcinoma (HCC). HCC an attractive target for immunotherapy as evidenced by active recruitment tumor-infiltrating lymphocytes that are capable lysing studies. DCs most potent antigen-presenting cells, capacity to take up, process, present antigens T stimulate...
This phase I/II study evaluated safety, efficacy, and pharmacokinetics of escalating, multiple doses siltuximab, a chimeric anti-interleukin (IL)-6 monoclonal antibody derived from new Chinese hamster ovary (CHO) cell line in patients with advanced/refractory solid tumors.In the I dose-escalation cohorts, 20 tumors received siltuximab 2.8 or 5.5 mg/kg every 2 weeks 11 15 3 intravenously (i.v.). In expansion (n = 24) II cohorts 40), Kirsten rat sarcoma-2 (KRAS)-mutant tumors, ovarian,...
Epstein-Barr virus (EBV) is associated with several malignancies including nasopharyngeal carcinoma, a high incidence tumor in Chinese populations, which cells express the two EBV antigens EB nuclear antigen 1 (EBNA1) and latent membrane protein 2 (LMP2). Here, we report phase I trial of recombinant vaccinia virus, MVA-EL, encodes an EBNA1/LMP2 fusion designed to boost T-cell immunity these antigens. The vaccine was delivered Hong Kong patients carcinoma determine safe immunogenic dose....
Abstract Purpose: Epstein–Barr virus (EBV) is associated with several cancers in which the tumor cells express EBV antigens EBNA1 and LMP2. A therapeutic vaccine comprising a recombinant vaccinia virus, MVA-EL, was designed to boost immunity these antigens. phase I trial conducted demonstrate safety immunogenicity of MVA-EL across range doses. Experimental Design: Sixteen patients United Kingdom (UK) EBV-positive nasopharyngeal carcinoma (NPC) received three intradermal vaccinations at...
This phase I study aimed to establish the biologic effects and MTD of agonistic IgG1 chimeric anti-CD40 antibody ChiLob7/4 in patients (pts) with a range CD40-expressing solid tumors diffuse large B-cell lymphoma, resistant conventional therapy. Potential mechanisms action for include direct cytotoxic on tumor cells conditioning antigen-presenting cells.
Abstract Background Cancer cachexia causes significant morbidity and mortality in advanced lung cancer patients. Clinical benefit of β-hydroxy-β-methylbutyrate, arginine, glutamine (HMB/Arg/Gln) was assessed newly diagnosed Methods NOURISH, a prospective, two-arm, open-label, multi-centre, randomised controlled phase II trial compared patients who received HMB/Arg/Gln with those did not. All structured nutritional, exercise symptom control via Macmillan Durham Cachexia Pack. Conducted five...
The relationship between primary and memory cytotoxic T lymphocyte (CTL) responses, the factors influencing entry into memory, are poorly understood. Here we address this in context of Epstein-Barr virus (EBV), a persistent human herpesvirus which CTL responses long-term carriers highly focused on epitopes preferentially drawn from just three eight available latent proteins, EBNAs 3A, 3B, 3C. To determine whether unusual level focusing is consequence challenge, carried out detailed analysis...
BACKGROUND.: Vaccination against Epstein-Barr virus (EBV), inducing an antibody response to the envelope glycoprotein gp350, might protect EBV-negative children with chronic kidney disease from lymphoproliferative after transplantation. METHODS.: A phase I trial recruited two successive cohorts given three injections of 12.5 microg (n=6) and 25 (n=10) recombinant gp350/alhydrogel vaccine over 6 8 weeks. RESULTS.: One in each cohort acquired wild EBV before week 28 evaluation. Both doses were...
Report results of patient-reported health-related quality life (HRQoL) and symptoms from phase III KEYNOTE-006 study pembrolizumab versus ipilimumab in patients with ipilimumab-naive advanced melanoma.Patients received 10 mg/kg every 2 (Q2W) or 3 weeks (Q3W) for up to years, four cycles Q3W. The European Organisation Research Treatment Cancer Quality Life Questionnaire C30 (EORTC QLQ-C30) was administered at baseline throughout the study. Patient-reported outcome (PRO) analyses were...
ABSTRACT Merkel cell carcinoma (MCC) is an aggressive skin cancer of neuroendocrine origin with a high propensity for recurrence and metastasis. polyomavirus (MCPyV) causes the majority MCC cases due to expression MCPyV small large tumor antigens (ST LT, respectively). Although number molecular mechanisms have been attributed antigen-mediated cellular transformation or replication, date, no studies investigated any potential link between T antigen highly metastatic nature MCC. Here we use...
Abstract Checkpoint inhibitor medications have revolutionized oncology practice, but frequently induce immune‐related adverse events. During autoimmune neurology practice over 20 months, we prospectively identified four patients with likely antibody‐mediated neurological diseases after checkpoint inhibitors: longitudinally extensive transverse myelitis, Guillain–Barré syndrome, and myasthenia gravis. All shared three characteristics: symptoms commenced 4 weeks drug administration, responses...
Aims The MAPK pathway is constitutively activated in uveal melanoma (UM). Selumetinib (AZD6244, ARRY-142886), a MEK inhibitor, has shown limited activity as monotherapy metastatic UM. Pre-clinical studies support synergistic cytotoxic for inhibitors combined with taxanes, and here we sought to assess the clinical efficacy of combining selumetinib paclitaxel. Patients Methods Seventy-seven patients UM who had not received prior chemotherapy were randomised alone, or paclitaxel without...
PURPOSE Approximately 50% of patients with advanced Merkel cell carcinoma (MCC) have primary or acquired resistance to PD-(L)1 blockade, which may be overcome using combination immune checkpoint inhibition (ICI) anti–cytotoxic T lymphocyte antigen-4 antibody. We present results from the recurrent/metastatic MCC cohort in CheckMate 358, a nonrandomized, multicohort, phase I/II study nivolumab (NIVO) without ipilimumab (IPI) virus-associated cancers (ClinicalTrials.gov identifier: NCT02488759...
ABSTRACT Virus-associated malignancies are potential targets for immunotherapeutic vaccines aiming to stimulate T-cell responses against viral antigens expressed in tumor cells. Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma, a high-incidence southern China, expresses limited set of EBV proteins, including the nuclear antigen EBNA1, an abundant source HLA class II-restricted CD4 + epitopes, and latent membrane protein LMP2, subdominant CD8 epitopes presented by I alleles common...