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Gene Therapy of X-Linked Severe Combined Immunodeficiency

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Abstract

Severe combined immunodeficiency (SCID) conditions appear to be the best possible candidates for a gene therapy approach. Transgene expression by lymphocyte precursors should confer to these cells a selective growth advantage that gives rise to long-lived T-lymphocytes. This rationale was used as a basis for a clinical trial of the SCID-X1 disorder caused by common γ (γc) gene mutations. This trial consists of ex vivo retroviral-mediated (MFG-B2 γc vector) γc gene transfer into marrow CD34+ cells in CH-296 fibronectin fragment—coated bags. Up to now, 9 patients with typical SCID-X1 diagnosed within the first year of life and lacking an HLA-identical donor have been enrolled. More than 2 years’ assessment of 5 patients and more than 1 year for 7 patients provide evidence for full development of functional, mature T-cells in the absence of any adverse effects. Functional transduced natural killer cells are also detectable, although in low numbers. All but 1 patient with T-cell immunity have also developed immunoglobulin production, which has alleviated the need for intravenous immunoglobulin substitution despite a low detection frequency of transduced B-cells. These 8 patients are doing well and living in a normal environment. This yet successful gene therapy demonstrates that in a setting where transgene expression provides a selective advantage, a clinical benefit can be expected.Int J Hematol. 2002;76:295-298.

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Author information

Correspondence to Salima Hacein-Bey-Abina or Alain Fischer or Marina Cavazzana-Calvoa.

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Hacein-Bey-Abina, S., Fischer, A. & Cavazzana-Calvoa, M. Gene Therapy of X-Linked Severe Combined Immunodeficiency. Int J Hematol 76, 295–298 (2002). https://doi.org/10.1007/BF02982686

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Key words

  • Gene transfer
  • γc Chain
  • SCID-X1
  • Selective advantage
  • Retroviral vector