title: Gene therapy of X-linked severe combined immunodeficiency.
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 gamma (gamma c) gene mutations. This trial consists of ex vivo retroviral-mediated (MFG-B2 gamma c vector) gammac 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.
authors.affiliation: INSERM U 429, Gene and Cell Therapy Unit, Hĵpital Necker Enfants Malades, Paris, France. sbey@wanadoo.fr
authors.forename: Salima
authors.initials: S
authors.lastname: Hacein-Bey-Abina
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana-Calvo
mesh_terms: D000818:Animals; D040181:Genetic Diseases, X-Linked / Q000628:therapy; D015316:Genetic Therapy / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D018123:Receptors, Interleukin / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000628:therapy*
chemical_list: D018123:Receptors, Interleukin