A5026879347- Hematopoietic Stem Cell Transplantation
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Chronic Myeloid Leukemia Treatments
- Lymphoma Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Polyomavirus and related diseases
- Acute Lymphoblastic Leukemia research
- Chronic Lymphocytic Leukemia Research
- Viral-associated cancers and disorders
- Renal Transplantation Outcomes and Treatments
- Virus-based gene therapy research
- Immunodeficiency and Autoimmune Disorders
- DNA Repair Mechanisms
- Mesenchymal stem cell research
- CRISPR and Genetic Engineering
- CNS Lymphoma Diagnosis and Treatment
- Vitamin D Research Studies
- Immune cells in cancer
- Adrenal Hormones and Disorders
- Multiple Myeloma Research and Treatments
- Blood disorders and treatments
Cancer Research UK Oxford Centre
2023-2025
National Institute for Health Research
2024
University of Oxford
1997-2024
Cellular Therapeutics (United Kingdom)
2024
MRC Weatherall Institute of Molecular Medicine
2020-2024
University of Birmingham
2001-2024
Medical Research Council
2021-2024
University College London
2013-2022
National Hospital for Neurology and Neurosurgery
2022
Royal Free London NHS Foundation Trust
2009-2022
The immunosuppressive activity of mesenchymal stromal cells (MSCs) is well documented. However, the therapeutic benefit completely unpredictable, thus raising concerns about MSC efficacy. One affecting factors unresolved conundrum that, despite being immunosuppressive, MSCs are undetectable after administration. Therefore, understanding fate infused could help predict clinical responses. Using a murine model graft-versus-host disease (GvHD), we demonstrate that actively induced to undergo...
Stem cell transplantation is used widely in the management of a range diseases hemopoietic system. Patients are immunosuppressed profoundly early posttransplant period, and reactivation cytomegalovirus (CMV) remains significant cause morbidity mortality. Adoptive transfer donor-derived CMV-specific CD8+ T clones has been shown to reduce rate viral reactivation; however, complexity this approach severely limits its clinical application. We have purified cells from blood stem transplant donors...
The functions of dendritic cells (DCs) are tightly regulated such that protective immune responses elicited and unwanted prevented. 1 alpha 25-dihydroxyvitamin D(3) (1 25(OH)(2)D(3)) has been identified as a major factor inhibits the differentiation maturation DCs, an effect dependent upon its binding to nuclear vitamin D receptor (VDR). Physiological control 25(OH)(2)D(3) levels is critically 25-hydroxyvitamin D(3)-1 alpha-hydroxylase OHase), mitochondrial cytochrome P450 enzyme catalyzes...
Bloom's syndrome (BS) is an autosomal recessive condition characterized by short stature, immunodeficiency, and a greatly elevated frequency of many types cancer. The gene mutated in BS, BLM, encodes protein containing seven "signature" motifs conserved wide range DNA RNA helicases. BLM most closely related to the subfamily DEXH box-containing helicases which prototypical member Escherichia coli RecQ. To analyze its biochemical properties, we have overexpressed oligohistidine-tagged version...
Summary Ageing is associated with evidence of immune deficiency and dysregulation. Key changes in the system ageing include a progressive reduction naive T cell output thymic involution peripheral expansion oligoclonal memory cells. These features are impaired responsiveness both vitro vivo, termed senescence. CD4+ CD25+ cells have recently been recognized as mediators regulation play role control autoimmune pathogen-specific responses. The significance regulatory context immunosenescence...
Chronic graft-versus-host disease (GVHD), a major complication of allogeneic stem-cell transplantation, becomes glucocorticoid-refractory or glucocorticoid-dependent in approximately 50% patients. Robust data from phase 3 randomized studies evaluating second-line therapy for chronic GVHD are lacking. In retrospective surveys, ruxolitinib, Janus kinase (JAK1–JAK2) inhibitor, showed potential efficacy patients with -dependent GVHD.
Background. Adoptive transfer of virus-specific T cells may accelerate reconstitution antigen-specific immunity and limit the morbidity mortality viral infections following allogeneic hematopoietic stem cell transplantation. The logistics producing has, however, limited application cellular therapies, particularly introduction more-recent regulatory stipulations. Methods. We investigated ability cytomegalovirus-specific cells, directly isolated from donor leucapheresates on basis interferon...
Transfer of T cells to freshly irradiated allogeneic recipients leads their rapid recruitment nonlymphoid tissues, where they induce graft-versus-host disease (GVHD). In contrast, when donor are transferred established mixed chimeras (MCs), GVHD is not induced despite a robust (GVH) reaction that eliminates normal and malignant host hematopoietic cells. We demonstrate here GVH-reactive MCs or mice undergo similar expansion activation, with up-regulation homing molecules required for entry...
The role of allogeneic transplantation with reduced-intensity conditioning in diffuse large B-cell lymphoma (DLBCL) is currently unclear, relatively little published data. We report the outcome (RIT) a cohort 48 consecutive patients relapsed/refractory DLBCL (30 de novo disease and 18 transformed follicular lymphoma) who underwent an alemtuzumab-containing regimen, median follow-up 52 months.Patients had experienced treatment failure five lines prior therapy, including autologous 69%, 17%...
Follicular lymphoma (FL) is an indolent disorder that treatable but considered incurable with chemotherapy alone. The curative potential of allogeneic transplantation using conventional myeloablative conditioning has been demonstrated, this approach precluded in the majority patients FL because excessive toxicity. Thus, reduced-intensity regimens are being explored.This study reports outcome 82 consecutive who underwent fludarabine, melphalan, and alemtuzumab for vivo T-cell depletion....
Purpose Reduced-intensity conditioning has minimized nonrelapse-related mortality rates after allogeneic transplantation in patients with Hodgkin's lymphoma, and relapse now become the major cause for treatment failure. We aimed to assess impact of donor lymphocyte infusions (DLIs) on incidence when administered mixed chimerism their utility as salvage therapy given relapse. Patients Methods This study reports outcomes 76 consecutive multiply relapsed or refractory lymphoma who underwent...
The liver contains both NK cells and their less cytotoxic relatives, ILC1. Here, we investigate the role of ILC1 in obesity-associated condition, non-alcoholic fatty disease (NAFLD). In livers mice suffering from NAFLD, are able to degranulate, express lower levels perforin kill cancerous target than those healthy animals. This is associated with a decreased ability cancer
BackgroundThe humoral and T-cell responses to booster COVID-19 vaccine types in multidisease immunocompromised individuals who do not generate adequate antibody two doses, is fully understood. The OCTAVE DUO trial aimed determine the value of third vaccinations a wide range patients with primary secondary immunodeficiencies.MethodsOCTAVE-DUO was prospective, open-label, multicentre, randomised, controlled, phase 3 investigating are following dose BNT162b2 or mRNA-1273, NVX-CoV2373 for those...
The role of donor lymphocyte infusion (DLI) in the management lymphoid malignancies after allogeneic stem cell transplantation (SCT) has not been clearly characterized. There is emerging evidence pointing to effectiveness this approach, particularly patients with low-grade disease, although date reported only small numbers patients, and thus utility treatment remains uncertain. A total 28 previously treated SCT received a 68 infusions lymphocytes. diagnoses were indolent non-Hodgkin lymphoma...