SUCCESSFUL PERIPHERAL T-LYMPHOCYTE-DIRECTED GENE-TRANSFER FOR A PATIENT WITH SEVERE COMBINED IMMUNE-DEFICIENCY CAUSED BY ADENOSINE-DEAMINASE DEFICIENCY

Ten patients with adenosine deaminase deficiency (ADA(-)) have been en rolled in gene therapy clinical trials since the first patient was tre ated in September 1990, We describe a Japanese ADA-severe combined imm une deficiency (SCID) patient who has received periodic infusions of g enetically modified autologous T lymphocytes transduced with the human ADA cDNA containing retroviral vector LASN, The percentage of periphe ral blood lymphocytes carrying the transduced ADA gene has remained st able 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 comparab le to those of a heterozygous carrier individual and was associated wi th increased T-lymphocyte counts and improvement of the patient's immu ne function. The results obtained in this trial are in agreement with previously published observations and support the usefulness of T lymp hocyte-directed gene transfer in the treatment of ADA-SCID. (C) 1998 b y The American Society of Hematology.