Development of gene therapy for immunodeficiency: adenosine deaminase deficiency.

Journal Article (Journal Article;Review)

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)

Full Text

Duke Authors

Cited Authors

  • Blaese, RM

Published Date

  • January 1, 1993

Published In

Volume / Issue

  • 33 / 1 Suppl

Start / End Page

  • S49 - S53

PubMed ID

  • 8433875

International Standard Serial Number (ISSN)

  • 0031-3998

Digital Object Identifier (DOI)

  • 10.1203/00006450-199305001-00278


  • eng

Conference Location

  • United States