X-linked chronic granulomatous disease (X-CGD) is an inherited immunodeficiency disease caused by a defect in the gp91phox gene encoding one of the subunits of the NADPH oxidase complex. NADPH oxidase plays an important role in eradicating the pathogen engulfed by the phagocytes. Therefore, CGD patients suffer from recurring life-threatening infection by bacteria or fungi, and die before 30 in most cases. In an effort to treat this life-threatening disease, we initiated a phase I/II gene therapy trial in 2007. Two X-CGD patients were enrolled in the trial. The retroviral vector used for gene delivery was the MLV-based MT vector containing gp91 phox cDNA (

Yu et al.,
Gene Ther
2000
;
7
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797
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Hong et al.,
J Gene Med
2004
;
6
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724
). Viral vectors have been produced from PG13 packaging cells in compliance with GMP. The clinical protocol was approved by the Korean FDA. G-CSF mobilized peripheral blood CD34+ cells were obtained from patients, and transduced in retronectin-coated gas-permeable bags containing SCGM media supplemented with SCF, FLT3L, TPO, and IL-3. The transduction efficiency was 10.5% for patient #1 and 28.5% for patient #2 when assessed by gp91 FACS analysis. Before receiving transduced cells, patients were treated with a conditioning regimen consisting of busulfan (3.2 mg/kg/day for 2 days) and fludarabine (40 mg/m2/day for 3 days). No adverse effects were observed from the use of busulfan and fludarabine. The percentage of superoxide-producing cells, as determined by DHR assay, was 6.4% and 14.5% at day 17, and decreased to less than 0.1% (after 1 year) and 0.4% (after 7 months). Thus far, abnormal cell expansion has not been observed.

Topics:
gene therapy, retroviridae, x-linked chronic granulomatous disease, busulfan, fludarabine, nadph oxidases, adverse effects, cd34 antigens, congenital immunodeficiency, cyclic gmp

Disclosures: Kim:ViroMed: Employment, Equity Ownership. Hong:ViroMed: Employment, Equity Ownership. Joo:ViroMed: Employment, Equity Ownership. Yoon:ViroMed: Employment, Equity Ownership. Kim:ViroMed: CEO, Equity Ownership.

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2008, The American Society of Hematology
2008
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