title: Successful peripheral T-lymphocyte-directed gene transfer for a patient with severe combined immune deficiency caused by adenosine deaminase deficiency.
abstract: Ten patients with adenosine deaminase deficiency (ADA-) have been enrolled in gene therapy clinical trials since the first patient was treated in September 1990. We describe a Japanese ADA- severe combined immune deficiency (SCID) patient who has received periodic infusions of genetically modified autologous T lymphocytes transduced with the human ADA cDNA containing retroviral vector LASN. The percentage of peripheral blood lymphocytes carrying the transduced ADA gene has remained stable at 10% to 20% during the 12 months since the fourth infusion. ADA enzyme activity in the patient's circulating T cells, which was only marginally detected before gene transfer, increased to levels comparable to those of a heterozygous carrier individual and was associated with increased T-lymphocyte counts and improvement of the patient's immune function. The results obtained in this trial are in agreement with previously published observations and support the usefulness of T lymphocyte-directed gene transfer in the treatment of ADA-SCID.
authors.affiliation: Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Onodera
authors.forename: T
authors.initials: T
authors.lastname: Ariga
authors.forename: N
authors.initials: N
authors.lastname: Kawamura
authors.forename: I
authors.initials: I
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Ohtsu
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: A
authors.initials: A
authors.lastname: Tame
authors.forename: H
authors.initials: H
authors.lastname: Furuta
authors.forename: M
authors.initials: M
authors.lastname: Okano
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
authors.forename: H
authors.initials: H
authors.lastname: Kotani
authors.forename: G J
authors.initials: GJ
authors.lastname: McGarrity
authors.forename: R M
authors.initials: RM
authors.lastname: Blaese
authors.forename: Y
authors.initials: Y
authors.lastname: Sakiyama
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics; D000917:Antibody Formation; D002478:Cells, Cultured / Q000637:transplantation; D002675:Child, Preschool; D003131:Combined Modality Therapy; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006388:Hemagglutinins / Q000097:blood; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D018655:Lymphocyte Count; D008297:Male; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D012882:Skin Tests; D013601:T-Lymphocytes / Q000201:enzymology / Q000637:transplantation*; D014162:Transfection; D014182:Transplantation, Autologous
chemical_list: D006388:Hemagglutinins; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D011993:Recombinant Fusion Proteins; D000243:Adenosine Deaminase