Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease.

@article{CavazzanaCalvo2000GeneTO,
  title={Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease.},
  author={Marina Cavazzana‐Calvo and Salima Hacein-Bey and Genevi{\`e}ve de Saint Basile and Fabian Gross and Eric S. Yvon and Patrick Nusbaum and F Selz and Christophe Hue and St{\'e}phanie Certain and Jean Laurent Casanova and Philippe Bousso and F. Le Deist and A M Fischer},
  journal={Science},
  year={2000},
  volume={288 5466},
  pages={
          669-72
        }
}
Severe combined immunodeficiency-X1 (SCID-X1) is an X-linked inherited disorder characterized by an early block in T and natural killer (NK) lymphocyte differentiation. This block is caused by mutations of the gene encoding the gammac cytokine receptor subunit of interleukin-2, -4, -7, -9, and -15 receptors, which participates in the delivery of growth, survival, and differentiation signals to early lymphoid progenitors. After preclinical studies, a gene therapy trial for SCID-X1 was initiated… Expand
Gene Therapy of X-Linked Severe Combined Immunodeficiency
TLDR
A successful gene therapy demonstrates that in a setting where transgene expression provides a selective advantage, a clinical benefit can be expected and is used as a basis for a clinical trial of the SCID-X1 disorder caused by common γ (γc) gene mutations. Expand
[Gene therapy of SCID-X1].
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Activation of cellular proto-oncogenes by accidental integration of the gene vector has been identified as the underlying mechanism and improved vector technology in combination with other protocol modifications may reduce the risk of this side effect. Expand
Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy.
TLDR
Ex vivo gene therapy with gamma(c) can safely correct the immune deficiency of patients with X-linked severe combined immunodeficiency and allow patients to have a normal life. Expand
Immune Reconstitution After Gene Therapy Approaches in Patients With X-Linked Severe Combined Immunodeficiency Disease
TLDR
This review provides an overview about the different gene therapy approaches used over the last 20 years to treat SCID-X1 patients, particularly focusing on lymphoid immune reconstitution, as well as the developments that have improved the process and outcomes. Expand
Assessing the risk of T-cell malignancies in mouse models of SCID-X1.
  • B. Sorrentino
  • Biology, Medicine
  • Molecular therapy : the journal of the American Society of Gene Therapy
  • 2010
TLDR
Most of the more than 30 treated patients have had full reconstitution of T-cell–mediated immunity, with restoration of B-cell function in fewer, but significant numbers of, cases, however, in both SCID-X1 trials, some patients developed T- cell malignancies that were clearly related to insertional mutagenesis from the integrated vector. Expand
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TLDR
Gene therapy has become an option for the treatment of 2 forms of severe combined immunodeficiency (SCID): X-linked SCID and adenosine deaminase deficiency and its safe and effective extension will have to be proved by examining the results of the ongoing clinical trials. Expand
Correction of canine X-linked severe combined immunodeficiency by in vivo retroviral gene therapy.
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This is the first demonstration that in vivo gene therapy targeting HSCs can restore both cellular and humoral immunity in a large-animal model of a fatal immunodeficiency, and achievement of durable immune reconstitution in XSCID dogs is demonstrated. Expand
Gene Therapy for Primary Immunodeficiencies: Current Status and Future Prospects
TLDR
This review details gene therapy trials for X-linked and adenosine deaminase-deficient severe combined immunodeficiency (SCID), Wiskott–Aldrich syndrome (WAS) and chronic granulomatous disease (CGD). Expand
Gene Therapy Studies in a Canine Model of X-Linked Severe Combined Immunodeficiency
TLDR
These studies demonstrate that durable T cell reconstitution and thymopoiesis with no evidence of any serious adverse events and, in contrast to the human XSCID patients, sustained marking in myeloid cells and B cells with Reconstitution of normal humoral immune function can be achieved for up to 5 years without any pretreatment conditioning. Expand
Gene Therapy for X-Linked Severe Combined Immunodeficiency: Where Do We Stand?
TLDR
The clinical experience of gene therapy for SCID-X1 is put into perspective, with the development and implementation of new generations of safer vectors such as self-inactivating gammaretroviral or lentiviral vectors as well as major advances in integrome knowledge. Expand
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