Gene Therapy of X-Linked Severe Combined Immunodeficiency

  • Salima Hacein-Bey-Abina
  • Alain Fischer
  • Marina Cavazzana-Calvoa
Progress in hematology


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.

Key words

Gene transfer γc Chain SCID-X1 Selective advantage Retroviral vector 


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Copyright information

© The Japanese Society of Hematology 2002

Authors and Affiliations

  • Salima Hacein-Bey-Abina
    • 1
    • 2
  • Alain Fischer
    • 1
    • 3
  • Marina Cavazzana-Calvoa
    • 1
    • 2
  1. 1.Inserm U 429Hôpital Necker Enfants MaladesParisFrance
  2. 2.Gene and Cell Therapy UnitHôpital Necker Enfants MaladesParisFrance
  3. 3.Unité d’Immunologie et d’Hématologie PédiatriquesHôpital Necker Enfants MaladesParisFrance

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