H Bobby Gaspar

Summary

Affiliation: University College London
Country: UK

Publications

  1. doi request reprint Hematopoietic stem cell gene therapy for adenosine deaminase-deficient severe combined immunodeficiency leads to long-term immunological recovery and metabolic correction
    H Bobby Gaspar
    Centre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London WC1N 1EH, UK
    Sci Transl Med 3:97ra80. 2011
  2. pmc How I treat ADA deficiency
    H Bobby Gaspar
    Centre for Immunodeficiency, Molecular Immunology Unit, University College London Institute of Child Health, London, United Kingdom
    Blood 114:3524-32. 2009
  3. pmc Kinase mutant Btk results in atypical X-linked agammaglobulinaemia phenotype
    H B Gaspar
    Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Clin Exp Immunol 120:346-50. 2000
  4. ncbi request reprint Gene therapy for severe combined immunodeficiencies
    H Bobby Gaspar
    Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK
    Expert Opin Biol Ther 5:1175-82. 2005
  5. ncbi request reprint Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning
    H Bobby Gaspar
    Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
    Mol Ther 14:505-13. 2006
  6. doi request reprint Bone marrow transplantation and alternatives for adenosine deaminase deficiency
    H Bobby Gaspar
    Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
    Immunol Allergy Clin North Am 30:221-36. 2010
  7. ncbi request reprint Successful treatment of lymphoproliferative disease complicating primary immunodeficiency/immunodysregulatory disorders with reduced-intensity allogeneic stem-cell transplantation
    Jonathan M Cohen
    Department of Clinical Immunology, Great Ormond Street Hospital, London, United Kingdom
    Blood 110:2209-14. 2007
  8. doi request reprint Long-term persistence of a polyclonal T cell repertoire after gene therapy for X-linked severe combined immunodeficiency
    H Bobby Gaspar
    Centre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London WC1N 1EH, UK
    Sci Transl Med 3:97ra79. 2011
  9. doi request reprint Self-inactivating gammaretroviral vectors for gene therapy of X-linked severe combined immunodeficiency
    Susannah I Thornhill
    Centre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Mol Ther 16:590-8. 2008
  10. pmc Lentiviral vectors containing an enhancer-less ubiquitously acting chromatin opening element (UCOE) provide highly reproducible and stable transgene expression in hematopoietic cells
    Fang Zhang
    Centre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London, United Kingdom
    Blood 110:1448-57. 2007

Detail Information

Publications48

  1. doi request reprint Hematopoietic stem cell gene therapy for adenosine deaminase-deficient severe combined immunodeficiency leads to long-term immunological recovery and metabolic correction
    H Bobby Gaspar
    Centre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London WC1N 1EH, UK
    Sci Transl Med 3:97ra80. 2011
    ..There were no adverse leukemic side effects. Thus, gene therapy for ADA-SCID is safe, with effective immunological and metabolic correction, and may offer a viable alternative to conventional unrelated donor HSCT...
  2. pmc How I treat ADA deficiency
    H Bobby Gaspar
    Centre for Immunodeficiency, Molecular Immunology Unit, University College London Institute of Child Health, London, United Kingdom
    Blood 114:3524-32. 2009
    ....
  3. pmc Kinase mutant Btk results in atypical X-linked agammaglobulinaemia phenotype
    H B Gaspar
    Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Clin Exp Immunol 120:346-50. 2000
    ..Together, these data may provide an explanation for the variable XLA phenotype...
  4. ncbi request reprint Gene therapy for severe combined immunodeficiencies
    H Bobby Gaspar
    Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK
    Expert Opin Biol Ther 5:1175-82. 2005
    ..These side effects are now being studied in detail and measures to prevent such events through alternative vectors delivery systems are in development at present...
  5. ncbi request reprint Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning
    H Bobby Gaspar
    Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
    Mol Ther 14:505-13. 2006
    ..No serious side effects were seen either as a result of the conditioning procedure or due to retroviral insertion. Gene therapy is an effective treatment option for the treatment of ADA-SCID...
  6. doi request reprint Bone marrow transplantation and alternatives for adenosine deaminase deficiency
    H Bobby Gaspar
    Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
    Immunol Allergy Clin North Am 30:221-36. 2010
    ..In this article the author reviews the available data on treatment by these different options, and offers an overview on when each of the different treatment options should be used...
  7. ncbi request reprint Successful treatment of lymphoproliferative disease complicating primary immunodeficiency/immunodysregulatory disorders with reduced-intensity allogeneic stem-cell transplantation
    Jonathan M Cohen
    Department of Clinical Immunology, Great Ormond Street Hospital, London, United Kingdom
    Blood 110:2209-14. 2007
    ..With careful monitoring and pre-emptive therapy, we advocate this RIC SCT approach to patients with PID who have pre-existing EBV-LPD...
  8. doi request reprint Long-term persistence of a polyclonal T cell repertoire after gene therapy for X-linked severe combined immunodeficiency
    H Bobby Gaspar
    Centre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London WC1N 1EH, UK
    Sci Transl Med 3:97ra79. 2011
    ..Further studies using vectors designed to limit mutagenesis and strategies to enhance B cell reconstitution are warranted to define the role of this treatment modality alongside conventional HSCT for SCID-X1...
  9. doi request reprint Self-inactivating gammaretroviral vectors for gene therapy of X-linked severe combined immunodeficiency
    Susannah I Thornhill
    Centre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Mol Ther 16:590-8. 2008
    ....
  10. pmc Lentiviral vectors containing an enhancer-less ubiquitously acting chromatin opening element (UCOE) provide highly reproducible and stable transgene expression in hematopoietic cells
    Fang Zhang
    Centre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London, United Kingdom
    Blood 110:1448-57. 2007
    ..These properties are achieved in the absence of classic enhancer activity and therefore may confer a high safety profile...
  11. ncbi request reprint Failure of SCID-X1 gene therapy in older patients
    Adrian J Thrasher
    Molecular Immunology Unit, Institute of Child Health, London, United Kingdom
    Blood 105:4255-7. 2005
    ..In particular, there is likely to be a limitation to initiation of normal thymopoiesis, and we therefore suggest that intervention for these patients should be considered as early as possible...
  12. ncbi request reprint Capture and generation of adenovirus specific T cells for adoptive immunotherapy
    Ilenia Chatziandreou
    Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Br J Haematol 136:117-26. 2007
    ..The protocols can be readily translated to generate ADV-specific T cells suitable for clinical use and offer an effective immunotherapeutic strategy to control ADV infection...
  13. ncbi request reprint Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector
    H Bobby Gaspar
    Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Lancet 364:2181-7. 2004
    ..We investigated the application of somatic gene therapy by use of a gibbon-ape-leukaemia-virus pseudotyped gammaretroviral vector...
  14. doi request reprint Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency
    Amel Hassan
    Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, United Kingdom
    Blood 120:3615-24; quiz 3626. 2012
    ..These data detail for the first time the outcomes of HCT for ADA-SCID and show that, if patients survive HCT, long-term cellular and humoral immune recovery is achieved...
  15. doi request reprint How I treat severe combined immunodeficiency
    H Bobby Gaspar
    Centre for Immunodeficiency, Molecular Immunology Unit, University College London Institute of Child Health, London, United Kingdom and
    Blood 122:3749-58. 2013
    ..These developments together with the advent of universal newborn screening for SCID should allow for a highly favorable outcome for this otherwise lethal condition. ..
  16. pmc SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease
    Christine Rivat
    Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, United Kingdom
    Blood 121:1073-6. 2013
    ..We demonstrate for the first time that HSC gene transfer corrects the cellular and humoral defects in SAP(-/-) mice providing proof of concept for gene therapy in XLP1...
  17. doi request reprint Haemopoietic stem-cell transplantation with antibody-based minimal-intensity conditioning: a phase 1/2 study
    Karin C Straathof
    Great Ormond Street Children s Hospital, London, UK
    Lancet 374:912-20. 2009
    ..We tested a novel antibody-based minimal-intensity conditioning (MIC) regimen to assess whether this approach allowed curative donor stem-cell engraftment without non-haemopoietic toxicity...
  18. ncbi request reprint Increased incidence of EBV-related disease following paediatric stem cell transplantation with reduced-intensity conditioning
    Jonathan Cohen
    Department of Bone Marrow Transplantation, Great Ormond Street Hospital NHS Trust, London, UK
    Br J Haematol 129:229-39. 2005
    ..This probably reflects the profound immunosuppression following RIC SCT, together with the incomplete ablation of recipient-derived B cells...
  19. ncbi request reprint Lentiviral vectors for T-cell suicide gene therapy: preservation of T-cell effector function after cytokine-mediated transduction
    Waseem Qasim
    Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Mol Ther 15:355-60. 2007
    ..We conclude that the use of interleukin-7 for lentiviral transduction offers the greatest potential for gene transfer to T cells without loss of function, and is favored for the clinical production of suicide gene modified T cells...
  20. doi request reprint Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening
    Lucinda Brown
    Department of Clinical Immunology, Great Ormond Street Hospital National Health Service Trust, London, UK
    Blood 117:3243-6. 2011
    ..Neonatal screening for SCID would significantly improve the outcome in this otherwise potentially devastating condition...
  21. pmc Update on clinical gene therapy in childhood
    Waseem Qasim
    Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Arch Dis Child 92:1028-31. 2007
    ..Minimising such risks through improved vector design will play an important role in developing the next generation of gene based therapies and extending their applicability...
  22. doi request reprint Cognitive and behavioral abnormalities in children after hematopoietic stem cell transplantation for severe congenital immunodeficiencies
    Penny Titman
    Department of Psychosocial Services, Great Ormond Street Hospital National Health Service NHS Trust, London, UK
    Blood 112:3907-13. 2008
    ..The specific genetic diagnosis, consanguinity, and severe clinical course are associated with poor outcome. Long-term follow-up of these patients should include screening to identify and manage these problems more effectively...
  23. ncbi request reprint Management options for adenosine deaminase deficiency; proceedings of the EBMT satellite workshop (Hamburg, March 2006)
    Claire Booth
    Molecular Immunology Unit, Institute of Child Health, University College London, and Department of Clinical Immunology, Great Ormond Street Hospital NHS Trust, London WC1N 3JH, UK
    Clin Immunol 123:139-47. 2007
    ..Long-term follow-up of treated patients highlights a significant incidence of non-immunological problems with cognitive, neurological and audiological abnormalities most prominent...
  24. ncbi request reprint Gene therapy for severe combined immunodeficiency due to adenosine deaminase deficiency
    Claudia A Montiel-Equihua
    Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, 30, Guilford Street, London WC1N 1EH, UK
    Curr Gene Ther 12:57-65. 2012
    ..In this document, we review the progress made so far in the development and establishment of gene therapy as an alternative form of treatment for ADA-SCID patients...
  25. doi request reprint Functional characterization of alloreactive T cells identifies CD25 and CD71 as optimal targets for a clinically applicable allodepletion strategy
    Sujith Samarasinghe
    Department of Molecular Immunology, Institute of Child Health, London, United Kingdom
    Blood 115:396-407. 2010
    ..39% vs third-party response of 62%, n = 5). This strategy enables further clinical studies of adoptive immunotherapy with larger doses of ADTs to enhance immune reconstitution after T cell-depleted stem cell transplantation...
  26. ncbi request reprint CD34 stem cell top-ups without conditioning after initial haematopoietic stem cell transplantation for correction of incomplete haematopoietic and immunological recovery in severe congenital immunodeficiencies
    Claire Booth
    Department of Clinical Immunology, Great Ormond Street Hospital NHS Trust, London, UK
    Br J Haematol 135:533-7. 2006
    ..Unconditioned stem cell boosts have limited toxicity but should be given early after the original graft to be effective...
  27. pmc The β-globin locus control region in combination with the EF1α short promoter allows enhanced lentiviral vector-mediated erythroid gene expression with conserved multilineage activity
    Claudia A Montiel-Equihua
    Centre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Mol Ther 20:1400-9. 2012
    ....
  28. ncbi request reprint Gene therapy: X-SCID transgene leukaemogenicity
    Adrian J Thrasher
    Molecular Immunology Unit, Institute of Child Health, University College London, London WC1N 1EH, UK
    Nature 443:E5-6; discussion E6-7. 2006
    ..Here we show that transgenic IL2RG does not necessarily have potent intrinsic oncogenic properties, and argue that the interpretation of this observation with respect to human trials is overstated...
  29. ncbi request reprint The impact of telomere erosion on memory CD8+ T cells in patients with X-linked lymphoproliferative syndrome
    Fiona J Plunkett
    Department of Immunology and Molecular Pathology, Royal Free and University College Medical School, London, UK
    Mech Ageing Dev 126:855-65. 2005
    ..This may contribute to the defective immunity found in XLP patients who survive acute EBV infection who develop EBV-related B cell lymphomas before the fourth decade of life...
  30. pmc Gene therapy for primary immunodeficiencies
    Christine Rivat
    UCL Institute of Child Health, Centre for Immunodeficiency, London WCIN 1EH, United Kingdom
    Hum Gene Ther 23:668-75. 2012
    ..In this review we summarize the status of these gene therapy trials and discuss the emerging application of similar strategies to other PIDs...
  31. ncbi request reprint Gene therapy for severe combined immune deficiency
    Waseem Qasim
    Molecular Immunology Unit, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK
    Expert Rev Mol Med 6:1-15. 2004
    ....
  32. pmc Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients
    Steven J Howe
    Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, University College London, London, United Kingdom
    J Clin Invest 118:3143-50. 2008
    ....
  33. pmc Sleeping beauty transposition from nonintegrating lentivirus
    Conrad A Vink
    Institute of Child Health, University College London, UK
    Mol Ther 17:1197-204. 2009
    ..Importantly, integration site analysis revealed redirection toward a profile mimicking SB-plasmid integration and away from integration within transcriptionally active genes favored by integrase-proficient lentiviral vectors (ILVs)...
  34. doi request reprint Gene therapy for primary immunodeficiency
    Claire Booth
    Molecular Immunology Unit, Centre of Immunodeficiency, Institute of Child Health, London, UK
    Curr Opin Pediatr 23:659-66. 2011
    ..Current strategies directed towards improving the efficacy and safety profile of gene therapy will be discussed...
  35. ncbi request reprint Improved survival after unrelated donor bone marrow transplantation in children with primary immunodeficiency using a reduced-intensity conditioning regimen
    Kanchan Rao
    Department of Bone Marrow Transplant, Great Ormond Street Hospital, London, United Kingdom
    Blood 105:879-85. 2005
    ....
  36. doi request reprint Autologous transplantation of amniotic fluid-derived mesenchymal stem cells into sheep fetuses
    S W Steven Shaw
    Prenatal Cell and Gene Therapy Group, Institute for Women s Health, University College London, London, UK
    Cell Transplant 20:1015-31. 2011
    ..Autologous cells derived from AF showed widespread organ migration and could offer an alternative way to ameliorate prenatal congenital disease...
  37. ncbi request reprint Autoimmune lymphoproliferative syndrome: molecular basis of disease and clinical phenotype
    Austen Worth
    Department of Clinical Immunology, Great Ormond Street Hospital NHS Trust, London, UK
    Br J Haematol 133:124-40. 2006
    ..This review provides a detailed insight into the pathophysiology of lymphocyte apoptosis and how this relates to the variable and complex clinical manifestations of ALPS...
  38. ncbi request reprint Gene therapy for lympho-hematopoietic disorders
    Adrian J Thrasher
    Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
    Curr Hematol Rep 4:305-9. 2005
    ..Recently, several clinical studies have shown that conventional gene transfer technology can produce major beneficial therapeutic effects...
  39. ncbi request reprint SAP mediates specific cytotoxic T-cell functions in X-linked lymphoproliferative disease
    Reza Sharifi
    Molecular Immunology Unit, Institute of Child Health, University College London, London, United Kingdom
    Blood 103:3821-7. 2004
    ..These studies demonstrate that in XLP the lack of SAP affects specific signaling pathways resulting in severe disruption of CTL function...
  40. doi request reprint The C76R transmembrane activator and calcium modulator cyclophilin ligand interactor mutation disrupts antibody production and B-cell homeostasis in heterozygous and homozygous mice
    Chiara Bacchelli
    Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, United Kingdom
    J Allergy Clin Immunol 127:1253-9.e13. 2011
    ..5% to 1% of healthy subjects. The contribution of the C104R mutation to the B-cell defects observed in patients with common variable immunodeficiency therefore remains unclear...
  41. pmc Pegademase bovine (PEG-ADA) for the treatment of infants and children with severe combined immunodeficiency (SCID)
    Claire Booth
    Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UK
    Biologics 3:349-58. 2009
    ..We also review the long-term outcome of patients receiving ERT and discuss the role of PEG-ADA in the management of infants and children with ADA-SCID, alongside other therapeutic options...
  42. ncbi request reprint Gene therapy in primary immunodeficiencies
    Adrian J Thrasher
    Molecular Immunology Unit, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK
    Expert Rev Clin Immunol 1:239-45. 2005
    ..New strategies to overcome these issues are likely to establish gene therapy as an efficacious strategy for many forms of primary immunodeficiencies...
  43. pmc Gammaretrovirus-mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo
    Kerstin Schwarzwaelder
    National Center for Tumor Diseases, German Cancer Research Center, Heidelberg, Germany
    J Clin Invest 117:2241-9. 2007
    ....
  44. pmc Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation
    Persis J Amrolia
    Department of Bone Marrow Transplantation, Great Ormond St Childrens Hospital, London WC1N 3JH, United Kingdom
    Blood 108:1797-808. 2006
    ..These data demonstrate that allodepleted donor T cells can be safely used to improve T-cell recovery after haploidentical SCT and may broaden the applicability of this approach...
  45. doi request reprint Abnormal expression of only the CD34 part of a transgenic CD34/herpes simplex virus-thymidine kinase fusion protein is associated with ganciclovir resistance
    Emad Bennour
    INSERM U645, 25020 Besançon, France
    Hum Gene Ther 19:699-709. 2008
    ..This is to our knowledge the first example of a loss of function of a FuProtein, of which one part is still expressed while the other one, suffering a selection pressure, is no longer detectable...
  46. ncbi request reprint Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry
    Juan J Sanchez
    Department of Forensic Genetics, Institute of Forensic Medicine, University of Copenhagen, DK 2100 Copenhagen, Denmark
    Ann Hum Genet 71:336-47. 2007
    ..ADA-SCID may be a frequent immunodeficiency disorder in Somalia, but will be underdiagnosed due to the prevailing socioeconomic and nutritional deprivation...
  47. ncbi request reprint Severe cutaneous papillomavirus disease after haematopoietic stem-cell transplantation in patients with severe combined immunodeficiency
    H Bobby Gaspar
    Br J Haematol 127:232-3. 2004
  48. ncbi request reprint Serial transplantation of mismatched donor hematopoietic cells between HLA-identical sibling pairs with congenital immunodeficiency: in vivo tolerance permits rapid immune reconstitution following T-replete transplantation without GVHD in the secondary re
    Jonathan M Cohen
    Department of Bone Marrow Transplantation, Great Ormond Street Hospital, Great Ormond Street, London WC1N 3JH, United Kingdom
    Blood 108:2124-6. 2006
    ....