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Pediatr Res. 1993 Jan;33(1 Suppl):S49-53; discussion S53-5.

Development of gene therapy for immunodeficiency: adenosine deaminase deficiency.

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  • 1Cellular Immunology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

Abstract

Deficiency of adenosine deaminase (ADA) results in severe combined immunodeficiency. Clinical cure has been observed in several ADA-severe combined immunodeficiency patients after bone marrow transplantation in which only donor T cells were engrafted, suggesting that T-cell correction alone is sufficient for full immune reconstitution. Children without an HLA-matched donor have been treated with polyethylene glycol-ADA as enzyme replacement therapy, resulting in varying degrees of immunologic and clinical improvement. In September 1990, we began treating a 4-y-old girl with periodic infusions of autologous culture-expanded T cells genetically corrected by insertion of a normal ADA gene using retroviral-mediated gene transfer with the LASN vector. After 2 y of polyethylene glycol-ADA 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 x 10(10) T cells, she has demonstrated a substantial increase in the number of circulating T cells (571/microL pre-gene therapy versus a mean of 1995/microL with gene therapy infusions every 6-8 wk) and the ADA activity in her peripheral blood T cells has increased > 10-fold. The increase in T-cell numbers and ADA activity has been associated with the development of positive delayed-type 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.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID:
8433875
[PubMed - indexed for MEDLINE]
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