title: Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease.
abstract: Severe combined immunodeficiency-X1 (SCID-X1) is an X-linked inherited disorder characterized by an early block in T and natural killer (NK) lymphocyte differentiation. This block is caused by mutations of the gene encoding the gammac cytokine receptor subunit of interleukin-2, -4, -7, -9, and -15 receptors, which participates in the delivery of growth, survival, and differentiation signals to early lymphoid progenitors. After preclinical studies, a gene therapy trial for SCID-X1 was initiated, based on the use of complementary DNA containing a defective gammac Moloney retrovirus-derived vector and ex vivo infection of CD34+ cells. After a 10-month follow-up period, gammac transgene-expressing T and NK cells were detected in two patients. T, B, and NK cell counts and function, including antigen-specific responses, were comparable to those of age-matched controls. Thus, gene therapy was able to provide full correction of disease phenotype and, hence, clinical benefit.
authors.affiliation: INSERM Unit 429, Gene Therapy Laboratory, Cell Therapy Laboratory, Unité d'Immunologie et d'Hématologie Pédiatriques, Hôpital Necker, 75743 Paris Cedex 15, France.
authors.forename: M
authors.initials: M
authors.lastname: Cavazzana-Calvo
authors.forename: S
authors.initials: S
authors.lastname: Hacein-Bey
authors.forename: G
authors.initials: G
authors.lastname: de Saint Basile
authors.forename: F
authors.initials: F
authors.lastname: Gross
authors.forename: E
authors.initials: E
authors.lastname: Yvon
authors.forename: P
authors.initials: P
authors.lastname: Nusbaum
authors.forename: F
authors.initials: F
authors.lastname: Selz
authors.forename: C
authors.initials: C
authors.lastname: Hue
authors.forename: S
authors.initials: S
authors.lastname: Certain
authors.forename: J L
authors.initials: JL
authors.lastname: Casanova
authors.forename: P
authors.initials: P
authors.lastname: Bousso
authors.forename: F L
authors.initials: FL
authors.lastname: Deist
authors.forename: A
authors.initials: A
authors.lastname: Fischer
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008979:Moloney murine leukemia virus / Q000235:genetics; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019076:Transgenes
chemical_list: D018952:Antigens, CD34; D007136:Immunoglobulins; D011948:Receptors, Antigen, T-Cell; D018123:Receptors, Interleukin