| Abstrakt: |
Deficiency of adenosine deaminase ADA results in severe combined immunodeficiency. Clinical cure has been observed in several ADAsevere combined immunodeficiency patients after bone marrow transplantation in which only donor T cells were engrafted, suggesting that Tcell correction alone is sufficient for full immune reconstitution. Children without an HLAmatched donor have been treated with polyethylene glycolADA as enzyme replacement therapy, resulting in varying degrees of immunologic and clinical improvement. In September 1990, we began treating a 4yold girl with periodic infusions of autologous cultureexpanded T cells genetically corrected by insertion of a normal ADA gene using retroviralmediated gene transfer with the LASN vector. After 2 y of polyethylene glycolADA treatment and before gene therapy, she continued to experience recurrent infections, was anergic and lymphopenic, and was deficient in isohemagglutinins. After seven infusions totaling 7 × 1010T cells, she has demonstrated a substantial increase in the number of circulating T cells 571L pregene therapyversusa mean of 1995L with gene therapy infusions every 6–8 wk and the ADA activity in her peripheral blood T cells has increased > 10fold. The increase in Tcell numbers and ADA activity has been associated with the development of positive delayedtype hypersensitivity skin tests, a significant increase in the level of isohemagglutinins, the regrowth of tonsils, and a decreased number of infectious illnesses. This improvement has persisted during suspension of treatment for more than 6 mo. A second patient treated since February 1991 has shown similar improvement in immune status. Both patients have tolerated the treatments without complication and are able to participate fully in school and social activities. These findings demonstrate that infusions of polyclonal autologous T cells metabolically corrected by ADA gene transfer can be an effective treatment for some children with ADAsevere combined immunodeficiency. Pediatr Res33 Suppl S49S55, 1993 |
