H. Bobby Gaspar
A5072838648- Virus-based gene therapy research
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Immunodeficiency and Autoimmune Disorders
- Cytomegalovirus and herpesvirus research
- Hematopoietic Stem Cell Transplantation
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Autoimmune and Inflammatory Disorders Research
- Parvovirus B19 Infection Studies
- Blood disorders and treatments
- Viral-associated cancers and disorders
- Adenosine and Purinergic Signaling
- Viral Infectious Diseases and Gene Expression in Insects
- Acute Lymphoblastic Leukemia research
- Pluripotent Stem Cells Research
- Polyomavirus and related diseases
- Lysosomal Storage Disorders Research
- Cellular Mechanics and Interactions
- Acute Myeloid Leukemia Research
- Viral gastroenteritis research and epidemiology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Peroxisome Proliferator-Activated Receptors
- Biomedical and Engineering Education
- Congenital Ear and Nasal Anomalies
University College London
2013-2022
Great Ormond Street Hospital
2011-2022
Great Ormond Street Hospital for Children NHS Foundation Trust
2013-2021
National Health Service
2004-2015
Hospital Prof. Dr. Fernando Fonseca
2015
Cell and Gene Therapy Catapult
2014
Blood Cancer UK
2013
Wellcome Trust
2013
Institute of Child Health
1998-2012
Boston Children's Hospital
2009
X-linked SCID (SCID-X1) is amenable to correction by gene therapy using conventional gammaretroviral vectors. Here, we describe the occurrence of clonal T cell acute lymphoblastic leukemia (T-ALL) promoted insertional mutagenesis in a completed trial 10 SCID-X1 patients. Integration vector an antisense orientation 35 kb upstream protooncogene LIM domain only 2 (LMO2) caused overexpression LMO2 leukemic clone. However, leukemogenesis was likely precipitated acquisition other genetic...
In X-linked adrenoleukodystrophy, mutations in ABCD1 lead to loss of function the ALD protein. Cerebral adrenoleukodystrophy is characterized by demyelination and neurodegeneration. Disease progression, which leads neurologic death, can be halted only with allogeneic hematopoietic stem-cell transplantation.We enrolled boys cerebral a single-group, open-label, phase 2-3 safety efficacy study. Patients were required have early-stage disease gadolinium enhancement on magnetic resonance imaging...
In previous clinical trials involving children with X-linked severe combined immunodeficiency (SCID-X1), a Moloney murine leukemia virus-based γ-retrovirus vector expressing interleukin-2 receptor γ-chain (γc) complementary DNA successfully restored immunity in most patients but resulted vector-induced through enhancer-mediated mutagenesis 25% of patients. We assessed the efficacy and safety self-inactivating retrovirus for treatment SCID-X1.
<h3>Importance</h3> Wiskott-Aldrich syndrome is a rare primary immunodeficiency associated with severe microthrombocytopenia. Partially HLA antigen–matched allogeneic hematopoietic stem cell (HSC) transplantation often curative but significant comorbidity. <h3>Objective</h3> To assess the outcomes and safety of autologous HSC gene therapy in syndrome. <h3>Design, Setting, Participants</h3> Gene-corrected HSCs were infused 7 consecutive patients lacking related or unrelated donors (age range,...
Gene therapy can restore immune and metabolic function in patients with adenosine deaminase immunodeficiency.
X-linked severe combined immunodeficiency (SCID-X1) is caused by mutations in the common cytokine receptor γ chain. These classically lead to complete absence of functional T and natural killer cell lineages as well intrinsically compromised B function. Although human leukocyte antigen (HLA)-matched hematopoietic stem transplantation (HSCT) highly successful SCID-X1 patients, HLA-mismatched procedures can be associated with prolonged immunodeficiency, graft-versus-host disease, increased...
Severe combined immunodeficiency due to adenosine deaminase (ADA) deficiency (ADA-SCID) is a rare and life-threatening primary immunodeficiency.
Abstract Patients with Wiskott–Aldrich syndrome (WAS) lacking a human leukocyte antigen-matched donor may benefit from gene therapy through the provision of gene-corrected, autologous hematopoietic stem/progenitor cells. Here, we present comprehensive, long-term follow-up results (median follow-up, 7.6 years) (phase I/II trial no. NCT02333760 ) for eight patients WAS having undergone phase lentiviral vector-based trials (nos. NCT01347346 and NCT01347242 ), focus on thrombocytopenia...
Gene therapy is a promising treatment option for monogenic diseases, but success has been seen in only handful of studies thus far. We now document successful reconstitution immune function child with the adenosine deaminase (ADA)-deficient form severe combined immunodeficiency (SCID) following hematopoietic stem cell (HSC) gene therapy. An ADA-SCID who showed poor response to PEG-ADA enzyme replacement was enrolled into clinical study. Following cessation therapy, autologous CD34+ HSCs were...
We treated 10 children with X-linked SCID (SCID-X1) using gammaretrovirus-mediated gene transfer. Those sufficient follow-up were found to have recovered substantial immunity in the absence of any serious adverse events up 5 years after treatment. To determine influence vector integration on lymphoid reconstitution, we compared retroviral sites (RISs) from peripheral blood CD3+ T lymphocytes patients taken between 9 and 30 months transplantation transduced CD34+ progenitor cells derived 1...
Abstract Ubiquitously acting chromatin opening elements (UCOEs) consist of methylation-free CpG islands encompassing dual divergently transcribed promoters housekeeping genes that have been shown to confer resistance transcriptional silencing and produce consistent stable transgene expression in tissue culture systems. To develop improved strategies for hematopoietic cell gene therapy, we assessed the potential novel human HNRPA2B1-CBX3 UCOE (A2UCOE) within context a self-inactivating (SIN)...
Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS).Twelve patients with cDGS underwent allogeneic cultured thymus.We sought to confirm and extend results previously obtained in single center.Two died pre-existing viral infections without having thymopoiesis, 1 late death occurred from autoimmune thrombocytopenia. One infant had septic shock shortly after transplantation, resulting graft loss need second transplant. Evidence...
Summary Adenovirus (AdV) infections are a frequent cause of morbidity and mortality following allogeneic stem cell transplantation (SCT), disseminated infection is associated with high mortality, particularly in paediatric SCT. Here, we describe an approach to reduce from adenoviraemia by combining prospective monitoring for the occurrence using sensitive polymerase chain reaction method, early antiviral therapy prompt withdrawal immunosuppression. A total 155 consecutive SCT procedures were...