T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years.
In 1990, a clinical trial was started using retroviral-mediated transfer of the adenosine deaminase (ADA) gene into the T cells of two children with severe combined immunodeficiency (ADA- SCID). The number of blood T cells normalized as did many cellular and humoral immune responses. Gene treatment ended after 2 years, but integrated vector and ADA gene expression in T cells persisted. Although many components remain to be perfected, it is concluded here that gene therapy can be a safe and effective addition to treatment for some patients with this severe immunodeficiency disease.
Blaese
R M
RM
National Center for Human Genome Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Culver
K W
KW
Miller
A D
AD
Carter
C S
CS
Fleisher
T
T
Clerici
M
M
Shearer
G
G
Chang
L
L
Chiang
Y
Y
Tolstoshev
P
P
Greenblatt
J J
JJ
Rosenberg
S A
SA
Klein
H
H
Berger
M
M
Mullen
C A
CA
Ramsey
W J
WJ
Muul
L
L
Morgan
R A
RA
Anderson
W F
WF
D000243:Adenosine Deaminase / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency* / Q000235:genetics* / Q000627:therapeutic use; D000917:Antibody Formation; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007111:Immunity, Cellular; D018655:Lymphocyte Count; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000201:enzymology; D008969:Molecular Sequence Data; D016511:Severe Combined Immunodeficiency / Q000201:enzymology / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology
D000243:Adenosine Deaminase; C051409:pegademase bovine