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Lentiviral gene therapy for X-linked chronic granulomatous disease.
Kohn, Donald B; Booth, Claire; Kang, Elizabeth M; Pai, Sung-Yun; Shaw, Kit L; Santilli, Giorgia; Armant, Myriam; Buckland, Karen F; Choi, Uimook; De Ravin, Suk See; Dorsey, Morna J; Kuo, Caroline Y; Leon-Rico, Diego; Rivat, Christine; Izotova, Natalia; Gilmour, Kimberly; Snell, Katie; Dip, Jinhua Xu-Bayford; Darwish, Jinan; Morris, Emma C; Terrazas, Dayna; Wang, Leo D; Bauser, Christopher A; Paprotka, Tobias; Kuhns, Douglas B; Gregg, John; Raymond, Hayley E; Everett, John K; Honnet, Geraldine; Biasco, Luca; Newburger, Peter E; Bushman, Frederic D; Grez, Manuel; Gaspar, H Bobby; Williams, David A; Malech, Harry L; Galy, Anne; Thrasher, Adrian J.
Afiliación
  • Kohn DB; University of California, Los Angeles, CA, USA. dkohn@mednet.ucla.edu.
  • Booth C; Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, UK.
  • Kang EM; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Pai SY; Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
  • Shaw KL; University of California, Los Angeles, CA, USA.
  • Santilli G; Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, UK.
  • Armant M; Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
  • Buckland KF; Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, UK.
  • Choi U; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • De Ravin SS; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Dorsey MJ; University of California, San Francisco, CA, USA.
  • Kuo CY; University of California, Los Angeles, CA, USA.
  • Leon-Rico D; Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, UK.
  • Rivat C; Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, UK.
  • Izotova N; Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, UK.
  • Gilmour K; Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, UK.
  • Snell K; Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, UK.
  • Dip JX; Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, UK.
  • Darwish J; Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, UK.
  • Morris EC; University College London Hospitals NHS Foundation Trust, London, UK.
  • Terrazas D; University of California, Los Angeles, CA, USA.
  • Wang LD; Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
  • Bauser CA; City of Hope, Beckman Research Institute, Duarte, CA, USA.
  • Paprotka T; Eurofins Genomics Sequencing Europe, Konstanz, Germany.
  • Kuhns DB; Eurofins Genomics Sequencing Europe, Konstanz, Germany.
  • Gregg J; Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
  • Raymond HE; University of Pennsylvania, Philadelphia, PA, USA.
  • Everett JK; University of Pennsylvania, Philadelphia, PA, USA.
  • Honnet G; University of Pennsylvania, Philadelphia, PA, USA.
  • Biasco L; Genethon, Evry, France.
  • Newburger PE; Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, UK.
  • Bushman FD; University of Massachusetts Medical School, Worcester, MA, USA.
  • Grez M; University of Pennsylvania, Philadelphia, PA, USA.
  • Gaspar HB; Georg-Speyer Haus, Frankfurt, Germany.
  • Williams DA; Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, UK.
  • Malech HL; Orchard Therapeutics, London, UK.
  • Galy A; Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
  • Thrasher AJ; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Nat Med ; 26(2): 200-206, 2020 02.
Article en En | MEDLINE | ID: mdl-31988463
Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells1,2. We report the initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34+ hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning in first-in-human studies (trial registry nos. NCT02234934 and NCT01855685). The primary objectives were to assess the safety and evaluate the efficacy and stability of biochemical and functional reconstitution in the progeny of engrafted cells at 12 months. The secondary objectives included the evaluation of augmented immunity against bacterial and fungal infection, as well as assessment of hematopoietic stem cell transduction and engraftment. Two enrolled patients died within 3 months of treatment from pre-existing comorbidities. At 12 months, six of the seven surviving patients demonstrated stable vector copy numbers (0.4-1.8 copies per neutrophil) and the persistence of 16-46% oxidase-positive neutrophils. There was no molecular evidence of either clonal dysregulation or transgene silencing. Surviving patients have had no new CGD-related infections, and six have been able to discontinue CGD-related antibiotic prophylaxis. The primary objective was met in six of the nine patients at 12 months follow-up, suggesting that autologous gene therapy is a promising approach for CGD patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia Genética / Lentivirus / Cromosomas Humanos X / Enfermedad Granulomatosa Crónica Tipo de estudio: Clinical_trials Límite: Adolescent / Adult / Child / Child, preschool / Humans / Male País/Región como asunto: America do norte / Europa Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia Genética / Lentivirus / Cromosomas Humanos X / Enfermedad Granulomatosa Crónica Tipo de estudio: Clinical_trials Límite: Adolescent / Adult / Child / Child, preschool / Humans / Male País/Región como asunto: America do norte / Europa Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos