UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Lentiviral gene therapy for X-linked chronic granulomatous disease

Kohn, DB; Booth, C; Kang, EM; Pai, S-Y; Shaw, KL; Santilli, G; Armant, M; ... the Net4CGD consortium; + view all (2020) Lentiviral gene therapy for X-linked chronic granulomatous disease. Nature Medicine , 26 pp. 200-206. 10.1038/s41591-019-0735-5. Green open access

[thumbnail of Merged PDF resub 9 December_XCGD.pdf]
Preview
Text
Merged PDF resub 9 December_XCGD.pdf - Accepted Version

Download (1MB) | Preview

Abstract

Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells. 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.

Type: Article
Title: Lentiviral gene therapy for X-linked chronic granulomatous disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41591-019-0735-5
Publisher version: https://doi.org/10.1038/s41591-019-0735-5
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Primary immunodeficiency disorders, Targeted gene repair
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10091213
Downloads since deposit
129Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item