A5008546894- Immune Cell Function and Interaction
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Tissue Engineering and Regenerative Medicine
- Hematopoietic Stem Cell Transplantation
- Cytomegalovirus and herpesvirus research
- Tracheal and airway disorders
- Electrospun Nanofibers in Biomedical Applications
- Immunotherapy and Immune Responses
- Biomedical Ethics and Regulation
- Mesenchymal stem cell research
- Virus-based gene therapy research
- Acute Myeloid Leukemia Research
- Monoclonal and Polyclonal Antibodies Research
- Pluripotent Stem Cells Research
- Chronic Lymphocytic Leukemia Research
- HIV Research and Treatment
- Cell death mechanisms and regulation
- Immunodeficiency and Autoimmune Disorders
- Dysphagia Assessment and Management
- Genetic Neurodegenerative Diseases
- RNA Interference and Gene Delivery
- Atherosclerosis and Cardiovascular Diseases
- Esophageal and GI Pathology
- Nanoparticle-Based Drug Delivery
University College London
2015-2024
The Royal Free Hospital
2013-2024
Roland Hill (United Kingdom)
2006-2024
CRUK Lung Cancer Centre of Excellence
2019-2023
Royal Free London NHS Foundation Trust
2011-2023
Universidad Autónoma de Madrid
2023
Westmead Hospital
2020-2022
Cancer Institute (WIA)
2022
London Women's Clinic
2020
Cellular Therapeutics (United Kingdom)
2007-2020
Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities. We examined the peripheral immune system found widespread evidence of innate activation detectable in plasma throughout course HD. Interleukin 6 levels were increased HD gene carriers with a mean 16 years before predicted onset clinical symptoms. To our knowledge, this earliest abnormality identified Monocytes from subjects expressed mutant huntingtin...
Cell replacement therapies for Parkinson's disease (PD) based on transplantation of pluripotent stem cell-derived dopaminergic neurons are now entering clinical trials. Here, we present quality, safety, and efficacy data supporting the first-in-human STEM-PD phase I/IIa trial along with design. The product was manufactured under GMP quality tested in vitro vivo to meet regulatory requirements. Importantly, no adverse effects were observed upon testing a 39-week rat GLP safety study toxicity,...
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...
To generate an ''off the shelf'' tissue-engineered heart valve, cells would need to be of allogeneic origin. Here, we report possibility using human bone marrow–derived mesenchymal stem (MSCs) as a suitable cell source for valves. Proliferative responses primary and primed CD4+ T MSCs were examined. A protein microarray system was used detect soluble factors from supernatants collected assays. are poor stimulators proliferation, despite provision B7-1 trans– co-stimulation. not only directly...
Decellularized (acellular) scaffolds, composed of natural extracellular matrix, form the basis an emerging generation tissue-engineered organ and tissue replacements capable transforming healthcare. Prime requirements for allogeneic, or xenogeneic, decellularized scaffolds are biocompatibility absence rejection. The humoral immune response to has been well documented, but there is a lack data on cell-mediated toward them in vitro vivo. Skeletal muscle were decellularized, characterized...
In 2010, a tissue-engineered trachea was transplanted into 10-year-old child using decellularized deceased donor repopulated with the recipient's respiratory epithelium and mesenchymal stromal cells. We report child's clinical progress, tracheal epithelialization costs over 4 years. A chronology of events derived from notes determined reference per procedure. Serial tracheoscopy images, lung function tests anti-HLA blood samples were compared. Epithelial morphology T cell, Ki67 cleaved...
Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system contributes to pathogenesis and has been targeted successfully modulate progression, but mechanistic understanding relating this mutant expression cells lacking. Here we demonstrate that human myeloid produce excessive inflammatory cytokines as result of cell-intrinsic effects expression. A direct effect on NFκB pathway, whereby it...
Abstract Tracheal replacement for the treatment of end-stage airway disease remains an elusive goal. The use tissue-engineered tracheae in compassionate cases suggests that such approach is a viable option. Here, stem cell-seeded, decellularized tracheal graft was used on basis girl with critical stenosis after conventional reconstructive techniques failed. represents first cell-seeded manufactured to full good manufacturing practice (GMP) standards. We report important preclinical and...
Prognosis for adult B-cell acute lymphoblastic leukemia (B-ALL) is poor, and there are currently no licensed CD19 chimeric antigen receptor (CAR) therapeutics. We developed a novel second-generation CD19-CAR (CAT19-41BB-Z) with fast off rate, designed more physiologic T-cell activation to reduce toxicity improve engraftment. describe the multicenter phase I ALLCAR19 (NCT02935257) study of autologous CAT19-41BB-Z CAR T cells (AUTO1) in relapsed or refractory (r/r) B-ALL.Patients age ≥ 16...
A tissue engineered oesophagus could overcome limitations associated with oesophageal substitution. Combining decellularized scaffolds patient-derived cells shows promise for regeneration of defects. In this proof-of-principle study, a two-stage approach generation bio-artificial graft addresses some major challenges in organ engineering, namely: (i) development multi-strata tubular structures, (ii) appropriate re-population/maturation constructs before transplantation, (iii)...
CD8+CD28– T cells are selectively expanded during viral infections, indicating their importance in anti-viral immune responses. Since little is known about the differentiation of cells, we investigated generation, function and survival characteristics this subset. In healthy individuals contained more elevated levels perforin IFN-γ than CD8+CD28+ subset, that they can have an effector function. were when activated cultured IL-2, IL-7 or IL-15. Moreover, generation was accelerated by type I...
The effects of the immunosuppressive drugs cyclosporin A and FK 506 were studied on cells chronically infected with human immunodeficiency virus type 1 (HIV-1) as well uninfected newly cells. When HIV-1 or HIV-2 cocultivated in presence there was a delay formation syncytia cytopathic effects. This inhibitory effect not due to decreased membrane expression CD4. In addition, an approximately 100-fold reduction yield infectious when grown these drugs, finding consistent other evidence HIV...
Summary. Although it has been known for more than 40 years that allogeneic immune responses cure leukaemias after bone marrow transplantation, autologous leukaemia‐specific immunity remains controversial and its impact upon survival not established. Here we have tested 25 patients with de novo acute leukaemias, while in remission at completion of their anti‐leukaemia therapy, evidence cytolytic to leukaemic cells taken cryopreserved disease presentation. We measured this degree cell‐mediated...
Natural killer (NK) cells are increasingly used in clinical studies order to treat patients with various malignancies. The following review summarizes platform lectures and 2013-2015 consortium meetings on manufacturing use of NK Europe United States. A broad overview recent pre-clinical results cell therapies is provided based unstimulated, cytokine-activated, as well genetically engineered using chimeric antigen receptors (CAR). Differences donor selection, quality control for cancer...
Patients with large tracheal lesions unsuitable for conventional endoscopic or open operations may require a replacement but there is no present consensus of how this be achieved. Tissue engineering using decellularized synthetic scaffolds offers new avenue airway reconstruction. Decellularized human donor have been applied in compassionate-use clinical cases naturally derived extracellular matrix (ECM) demand lengthy preparation times. Here, we compare clinically detergent-enzymatic method...
Abstract Stem cell tracking in cellular therapy and regenerative medicine is an urgent need, superparamagnetic iron oxide nanoparticles (IONPs) could be used as contrast agents magnetic resonance imaging (MRI) that allows visualization of the implanted cells ensuring they reach desired sites vivo . Herein, we report study interaction 3,4-dihydroxyhydrocinnamic acid (DHCA) functionalized IONPs have desirable properties for T 2 - weighted MRI, with bone marrow-derived primary human mesenchymal...