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Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector.

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Title: Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector.
Authors: Gaspar HB (AUTHOR), Parsley KL (AUTHOR), Howe S (AUTHOR), King D (AUTHOR), Gilmour KC (AUTHOR), Sinclair J (AUTHOR), Brouns G (AUTHOR), Schmidt M (AUTHOR), Von Kalle C (AUTHOR), Barington T (AUTHOR), Jakobsen MA (AUTHOR), Christensen HO (AUTHOR), Al Ghonaium A (AUTHOR), White HN (AUTHOR), Smith JL (AUTHOR), Levinsky RJ (AUTHOR), Ali RR (AUTHOR), Kinnon C (AUTHOR), Thrasher AJ (AUTHOR), Gaspar, H Bobby (AUTHOR)
Source: Lancet. 12/18/2004, Vol. 364 Issue 9452, p2181-2187. 7p.
Abstract: Background: X-linked severe combined immunodeficiency (SCID-X1) is caused by mutations in the common cytokine-receptor gamma chain (gamma(c)), resulting in disruption of development of T lymphocytes and natural-killer cells. B-lymphocyte function is also intrinsically compromised. Allogeneic bone-marrow transplantation is successful if HLA-matched family donors are available, but HLA-mismatched procedures are associated with substantial morbidity and mortality. We investigated the application of somatic gene therapy by use of a gibbon-ape-leukaemia-virus pseudotyped gammaretroviral vector.Methods: Four children with SCID-X1 were enrolled. Autologous CD34-positive haemopoietic bone-marrow stem cells were transduced ex vivo and returned to the patients without preceding cytoreductive chemotherapy. The patients were monitored for integration and expression of the gamma(c) vector and for functional immunological recovery.Findings: All patients have shown substantial improvements in clinical and immunological features, and prophylactic medication could be withdrawn in two. No serious adverse events have been recorded. T cells responded normally to mitogenic and antigenic stimuli, and the T-cell-receptor (TCR) repertoire was highly diverse. Where assessable, humoral immunity, in terms of antibody production, was also restored and associated with increasing rates of somatic mutation in immunoglobulin genes.Interpretation: Gene therapy for SCID-X1 is a highly effective strategy for restoration of functional cellular and humoral immunity. [ABSTRACT FROM AUTHOR]
Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector.
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  Data: <searchLink fieldCode="AR" term="%22Gaspar+HB%22">Gaspar HB</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Parsley+KL%22">Parsley KL</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Howe+S%22">Howe S</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22King+D%22">King D</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gilmour+KC%22">Gilmour KC</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sinclair+J%22">Sinclair J</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Brouns+G%22">Brouns G</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Schmidt+M%22">Schmidt M</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Von+Kalle+C%22">Von Kalle C</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Barington+T%22">Barington T</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Jakobsen+MA%22">Jakobsen MA</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Christensen+HO%22">Christensen HO</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Al+Ghonaium+A%22">Al Ghonaium A</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22White+HN%22">White HN</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Smith+JL%22">Smith JL</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Levinsky+RJ%22">Levinsky RJ</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ali+RR%22">Ali RR</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kinnon+C%22">Kinnon C</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Thrasher+AJ%22">Thrasher AJ</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gaspar%2C+H+Bobby%22">Gaspar, H Bobby</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Lancet%22">Lancet</searchLink>. 12/18/2004, Vol. 364 Issue 9452, p2181-2187. 7p.
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  Data: <bold>Background: </bold>X-linked severe combined immunodeficiency (SCID-X1) is caused by mutations in the common cytokine-receptor gamma chain (gamma(c)), resulting in disruption of development of T lymphocytes and natural-killer cells. B-lymphocyte function is also intrinsically compromised. Allogeneic bone-marrow transplantation is successful if HLA-matched family donors are available, but HLA-mismatched procedures are associated with substantial morbidity and mortality. We investigated the application of somatic gene therapy by use of a gibbon-ape-leukaemia-virus pseudotyped gammaretroviral vector.<bold>Methods: </bold>Four children with SCID-X1 were enrolled. Autologous CD34-positive haemopoietic bone-marrow stem cells were transduced ex vivo and returned to the patients without preceding cytoreductive chemotherapy. The patients were monitored for integration and expression of the gamma(c) vector and for functional immunological recovery.<bold>Findings: </bold>All patients have shown substantial improvements in clinical and immunological features, and prophylactic medication could be withdrawn in two. No serious adverse events have been recorded. T cells responded normally to mitogenic and antigenic stimuli, and the T-cell-receptor (TCR) repertoire was highly diverse. Where assessable, humoral immunity, in terms of antibody production, was also restored and associated with increasing rates of somatic mutation in immunoglobulin genes.<bold>Interpretation: </bold>Gene therapy for SCID-X1 is a highly effective strategy for restoration of functional cellular and humoral immunity. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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