Trial reportThe Journal of allergy and clinical immunology2015
B-cell reconstitution after lentiviral vector-mediated gene therapy in patients with Wiskott-Aldrich syndrome.
Trial report in The Journal of allergy and clinical immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- Lentiviral haemopoietic stem/progenitor cell gene therapy for treatment of Wiskott-Aldrich syndrome: interim results of a non-randomised, open-label, phase 1/2 clinical study.The Lancet. Haematology · 2019Trial
- Viral-based gene therapy clinical trials for immune deficiencies and blood disorders from 2013 until 2023 - an overview.Regenerative therapy · 2025Review
- Advances in Genetic Reprogramming: Prospects from Developmental Biology to Regenerative Medicine.Current medicinal chemistry · 2024Review
- Long-term safety and efficacy of lentiviral hematopoietic stem/progenitor cell gene therapy for Wiskott-Aldrich syndrome.Nature medicine · 2022Article
- Article
- Intrathymic adeno-associated virus gene transfer rapidly restores thymic function and long-term persistence of gene-corrected T cells.The Journal of allergy and clinical immunology · 2020Article
- Gene Modification and Three-Dimensional Scaffolds as Novel Tools to Allow the Use of Postnatal Thymic Epithelial Cells for Thymus Regeneration Approaches.Stem cells translational medicine · 2019Article
- Gene therapy targeting haematopoietic stem cells for inherited diseases: progress and challenges.Nature reviews. Drug discovery · 2019Review
- How I manage patients with Wiskott Aldrich syndrome.British journal of haematology · 2019Review
- A Cetuximab-Mediated Suicide System in Chimeric Antigen Receptor-Modified Hematopoietic Stem Cells for Cancer Therapy.Human gene therapy · 2019Article
- Cryopreservation of Human Adipose-Derived Stem Cells for Use inHuman gene therapy methods · 2018Article
- T-cell defects in patients withBlood · 2018Article
- Neutrophils drive type I interferon production and autoantibodies in patients with Wiskott-Aldrich syndrome.The Journal of allergy and clinical immunology · 2018Article
- Absence of Replication-Competent Lentivirus in the Clinic: Analysis of Infused T Cell Products.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Optimization of lentiviral vector production for scale-up in fixed-bed bioreactor.Gene therapy · 2018Article
- Clinical Manifestations and Pathophysiological Mechanisms of the Wiskott-Aldrich Syndrome.Journal of clinical immunology · 2018Review
- A map of human circular RNAs in clinically relevant tissues.Journal of molecular medicine (Berlin, Germany) · 2017Article
- Quantitative Imaging Approaches to Study the CAR Immunological Synapse.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Review
- Genetic Engineering and Manufacturing of Hematopoietic Stem Cells.Molecular therapy. Methods & clinical development · 2017Review
- Safe and Effective Gene Therapy for Murine Wiskott-Aldrich Syndrome Using an Insulated Lentiviral Vector.Molecular therapy. Methods & clinical development · 2017Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundWiskott-Aldrich syndrome (WAS) is a severe X-linked immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, and susceptibility to autoimmunity and lymphomas. Hematopoietic stem cell transplantation is the treatment of choice; however, administration of WAS gene-corrected autologous hematopoietic stem cells has been demonstrated as a feasible alternative therapeutic approach.
objectiveBecause B-cell homeostasis is perturbed in patients with WAS and restoration of immune competence is one of the main therapeutic goals, we have evaluated reconstitution of the B-cell compartment in 4 patients who received autologous hematopoietic stem cells transduced with lentiviral vector after a reduced-intensity conditioning regimen combined with anti-CD20 administration.
methodsWe evaluated B-cell counts, B-cell subset distribution, B cell-activating factor and immunoglobulin levels, and autoantibody production before and after gene therapy (GT). WAS gene transfer in B cells was assessed by measuring vector copy numbers and expression of Wiskott-Aldrich syndrome protein.
resultsAfter lentiviral vector-mediated GT, the number of transduced B cells progressively increased in the peripheral blood of all patients. Lentiviral vector-transduced progenitor cells were able to repopulate the B-cell compartment with a normal distribution of B-cell subsets both in bone marrow and the periphery, showing a WAS protein expression profile similar to that of healthy donors. In addition, after GT, we observed a normalized frequency of autoimmune-associated CD19(+)CD21(-)CD35(-) and CD21(low) B cells and a reduction in B cell-activating factor levels. Immunoglobulin serum levels and autoantibody production improved in all treated patients.
conclusionsWe provide evidence that lentiviral vector-mediated GT induces transgene expression in the B-cell compartment, resulting in ameliorated B-cell development and functionality and contributing to immunologic improvement in patients with WAS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.