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Updated: Dec 29, 2025
Lentiviral Vector-mediated Gene Therapy of Hepatocytes Ex Vivo for Autologous Transplantation in Swine
Published on: November 4, 2018
Lentiviral gene therapy for X-linked chronic granulomatous disease
Donald B Kohn1, Claire Booth2, Elizabeth M Kang3
1University of California, Los Angeles, CA, USA. dkohn@mednet.ucla.edu.
Insights
Gene therapy using lentiviral gene transfer shows promise for X-linked chronic granulomatous disease (X-CGD). Six of seven surviving patients achieved stable reconstitution and reduced infections after 12 months.
Area of Science:
- Hematology
- Immunology
- Gene Therapy
Background:
- Chronic granulomatous disease (CGD) is a rare inherited disorder affecting phagocytic cells.
- X-linked CGD (X-CGD) is the most common form, leading to severe immune deficiencies.
- Current treatments are limited, highlighting the need for novel therapeutic strategies.
Purpose of the Study:
- To assess the safety and efficacy of ex vivo autologous CD34+ hematopoietic stem and progenitor cell-based lentiviral gene therapy in X-CGD patients.
- To evaluate biochemical and functional reconstitution, augmented immunity, and hematopoietic stem cell engraftment at 12 months post-treatment.
Main Methods:
- Nine severely affected X-CGD patients received myeloablative conditioning followed by autologous lentiviral gene therapy.
- Safety, vector copy numbers, neutrophil oxidase function, and clinical outcomes were monitored.
- Assessments included transduction, engraftment, and immune reconstitution against bacterial and fungal infections.
Main Results:
- Six of seven surviving patients showed stable vector copy numbers and significant persistence of oxidase-positive neutrophils at 12 months.
- Surviving patients experienced no new CGD-related infections, with six discontinuing antibiotic prophylaxis.
- No evidence of clonal dysregulation or transgene silencing was observed in treated patients.
Conclusions:
- Autologous lentiviral gene therapy is a safe and promising approach for treating X-linked chronic granulomatous disease.
- The treatment led to significant functional immune reconstitution and reduced infection rates in surviving patients.
- This gene therapy strategy offers a potential curative option for individuals with severe X-CGD.
Abstract:
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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