Gene Therapy of X-Linked Severe Combined Immunodeficiency

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

DOI: 10.1007/BF02982686

Cite this article as:
Hacein-Bey-Abina, S., Fischer, A. & Cavazzana-Calvoa, M. Int J Hematol (2002) 76: 295. doi:10.1007/BF02982686

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.

Key words

Gene transfer γc Chain SCID-X1 Selective advantage Retroviral vector 

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
  4. 4.Laboratoire de Thérapie Cellulaire et GéniqueINSERM U429, Hôpital Necker Enfants MaladesParisFrance

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