Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency.

Autor:	Cicalese MP; San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy;, Ferrua F; San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy;, Castagnaro L; San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy;, Pajno R; Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy;, Barzaghi F; San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy;, Giannelli S; San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy;, Dionisio F; San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy;, Brigida I; San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy;, Bonopane M; San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy;, Casiraghi M; San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy;, Tabucchi A; Department of Medical Biotechnology, University of Siena, Siena, Italy;, Carlucci F; Department of Medical Biotechnology, University of Siena, Siena, Italy;, Grunebaum E; Division of Immunology and Allergy, The Hospital for Sick Children, Toronto, Canada;, Adeli M; Division of Immunology and Allergy, Hamad Medical Corporation, Doha, Qatar;, Bredius RG; Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands;, Puck JM; Department of Pediatrics, University of California-San Francisco, San Francisco, CA;, Stepensky P; Pediatric Hematology-Oncology and Bone Marrow Transplantation, Hadassah Hebrew University Hospital, Jerusalem, Israel;, Tezcan I; Department of Pediatrics, Section of Pediatric Immunology, Hacettepe University Faculty of Medicine, Ankara, Turkey;, Rolfe K; GSK Research and Development, GlaxoSmithKline, Stevenage, United Kingdom, and Upper Merion, PA;, De Boever E; GSK Research and Development, GlaxoSmithKline, Stevenage, United Kingdom, and Upper Merion, PA;, Reinhardt RR; GSK Research and Development, GlaxoSmithKline, Stevenage, United Kingdom, and Upper Merion, PA;, Appleby J; GSK Research and Development, GlaxoSmithKline, Stevenage, United Kingdom, and Upper Merion, PA;, Ciceri F; Vita-Salute San Raffaele University, Milan, Italy; Hematology and Bone Marrow Transplant Unit, San Raffaele Scientific Institute, Milan, Italy; and., Roncarolo MG; San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; Department of Pediatrics Division of Stem Cell Transplantation and Regenerative Medicine, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA., Aiuti A; San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy;
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2016 Jul 07; Vol. 128 (1), pp. 45-54. Date of Electronic Publication: 2016 Apr 29.
DOI:	10.1182/blood-2016-01-688226
Abstrakt:	Adenosine deaminase (ADA) deficiency is a rare, autosomal-recessive systemic metabolic disease characterized by severe combined immunodeficiency (SCID). The treatment of choice for ADA-deficient SCID (ADA-SCID) is hematopoietic stem cell transplant from an HLA-matched sibling donor, although <25% of patients have such a donor available. Enzyme replacement therapy (ERT) partially and temporarily relieves immunodeficiency. We investigated the medium-term outcome of gene therapy (GT) in 18 patients with ADA-SCID for whom an HLA-identical family donor was not available; most were not responding well to ERT. Patients were treated with an autologous CD34(+)-enriched cell fraction that contained CD34(+) cells transduced with a retroviral vector encoding the human ADA complementary DNA sequence (GSK2696273) as part of single-arm, open-label studies or compassionate use programs. Overall survival was 100% over 2.3 to 13.4 years (median, 6.9 years). Gene-modified cells were stably present in multiple lineages throughout follow up. GT resulted in a sustained reduction in the severe infection rate from 1.17 events per person-year to 0.17 events per person-year (n = 17, patient 1 data not available). Immune reconstitution was demonstrated by normalization of T-cell subsets (CD3(+), CD4(+), and CD8(+)), evidence of thymopoiesis, and sustained T-cell proliferative capacity. B-cell function was evidenced by immunoglobulin production, decreased intravenous immunoglobulin use, and antibody response after vaccination. All 18 patients reported infections as adverse events; infections of respiratory and gastrointestinal tracts were reported most frequently. No events indicative of leukemic transformation were reported. Trial details were registered at www.clinicaltrials.gov as #NCT00598481. (© 2016 by The American Society of Hematology.)
Databáze:	MEDLINE
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