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Retroviral gene therapy for X-linked chronic granulomatous disease: results from phase I/II trial

X-linked chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by a defect in the gp91phox gene. In an effort to treat X-CGD, we investigated the safety and efficacy of gene therapy using a retroviral vector, MT-gp91. Two X-CGD patients received autologous CD34+ cells transduce...

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Main Authors: Kang, Hyoung Jin (Author) , Bartholomä, Cynthia C. (Author) , Paruzynski, Anna (Author) , Arens, Anne (Author) , Kim, Sujeong (Author) , Yu, Seung Shin (Author) , Hong, Youngtae (Author) , Joo, Chang-Wan (Author) , Yoon, Nam-Kyung (Author) , Rhim, Jung-Woo (Author) , Kim, Joong Gon (Author) , Kalle, Christof von (Author) , Schmidt, Manfred (Author) , Kim, Sunyoung (Author) , Ahn, Hyo Seop (Author)
Format: Article (Journal)
Language:English
Published: 30 August 2011
In: Molecular therapy
Year: 2011, Volume: 19, Issue: 11, Pages: 2092-2101
ISSN:1525-0024
DOI:10.1038/mt.2011.166
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/mt.2011.166
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1525001616328076
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Author Notes:Hyoung Jin Kang, Cynthia C Bartholomae, Anna Paruzynski, Anne Arens, Sujeong Kim, Seung Shin Yu, Youngtae Hong, Chang-Wan Joo, Nam-Kyung Yoon, Jung-Woo Rhim, Joong Gon Kim, Christof Von Kalle, Manfred Schmidt, Sunyoung Kim and Hyo Seop Ahn
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Summary:X-linked chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by a defect in the gp91phox gene. In an effort to treat X-CGD, we investigated the safety and efficacy of gene therapy using a retroviral vector, MT-gp91. Two X-CGD patients received autologous CD34+ cells transduced with MT-gp91 after a conditioning regimen consisting of fludarabine and busulfan. The level of gene-marked cells was highest at day 21 (8.3 and 11.7% in peripheral blood cells) but decreased to 0.08 and 0.5%, respectively, 3 years after gene transfer. The level of functionally corrected cells, as determined by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase assay, reached a peak at day 17 (6.5% patient 1 (P1) and 14.3% patient 2 (P2) of total granulocytes) and declined to 0.05% (P1) and 0.21% (P2), 3 years later. Some retroviral vectors were found to have integrated within or close to the proto-oncogenes MDS1-EVI1, PRDM16, and CCND2; however, no abnormal cell expansion or related hematological malignancy was observed. Overall, the gene transfer procedure did not produce any serious adverse effects and was able to convert a significant fraction of blood cells to biologically functional cells, albeit for a short period of time.
Item Description:Gesehen am 11.07.2022
Physical Description:Online Resource
ISSN:1525-0024
DOI:10.1038/mt.2011.166

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