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A Serious Adverse Event after Successful Gene Therapy for X-Linked Severe Combined Immunodeficiency
Abstract
To the Editor: We recently reported (April 18 issue)1 the sustained correction of X-linked severe combined immunodeficiency disease by ex vivo, retrovirally mediated transfer of the γc gene into CD34+ cells in four of five patients with the disease. These results have since been confirmed in four additional patients with typical X-linked severe combined immunodeficiency. Of the first four successfully treated patients, three continue to do well up to 3.6 years after gene therapy, whereas a serious adverse event occurred in the fourth patient. At a routine checkup 30 months after gene therapy, lymphocytosis consisting of a monoclonal population . . .
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“Lentiviral vectors are considered safer than gamma-retroviral vectors in terms of their semi-random integration patterns, as gene integration does not preferentially occur in start regions of active genes (93-95).”
From Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy (2021) · cites this paper as [93]
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“While the majority of patients experienced successful restoration of immune function (163), several patients developed a T-cell lymphoproliferative disease (164) caused by an activating insertional mutation event in the LMO2 proto-oncogene (165).”
Background
Metadata
- Authors
- Hacein-Bey-Abina, S., von Kalle, C., Schmidt, M., Le Deist, F., Wulffraat, N., McIntyre, E., Radford, I., Villeval, J.-L., Fraser, C. C., Cavazzana-Calvo, M., & Fischer, A.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2003-01-16
- Volume
- 348
- Issue
- 3
- Pages
- 255-256
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2323613689
- Cited by
- 1,867
- References
- 0
- Citations by year
- 2026: 29 · 2025: 32 · 2024: 31 · 2023: 25 · 2022: 47 · 2021: 52 · 2020: 46 · 2019: 50 · 2018: 45 · 2017: 63 · 2016: 65 · 2015: 84 · 2014: 87 · 2013: 92 · 2012: 92
- FWCI
- 86.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- DigitalGeorgetown (Georgetown University Library) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Keywords
- X-linked severe combined immunodeficiency, gene therapy, adverse events, gene therapy safety
- MeSH terms
- Chromosomes, Human, Pair 11, DNA-Binding Proteins, Humans, Genetic Linkage, Metalloproteins, Proto-Oncogene Proteins, Retroviridae, Genetic Therapy, Gene Expression, Mutagenesis, Insertional, Severe Combined Immunodeficiency, Lymphocyte Count, Chromosomes, Human, X, Adaptor Proteins, Signal Transducing, Precursor Cell Lymphoblastic Leukemia-Lymphoma, LIM Domain Proteins
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