T Lymphocyte-Directed Gene Therapy for ADA
SCID:
Initial Trial Results After 4 Years
R. Michael Blaese (1),
Kenneth W. Culver,
A. Dusty Miller,
Charles S. Carter,
Thomas Fleisher,
Mario Clerici (2),
Gene Shearer,
Lauren Chang,
Yawen Chiang,
Paul Tolstoshev,
Jay J. Greenblatt,
Steven A. Rosenberg,
Harvey Klein,
Melvin Berger,
Craig A. Mullen (3),
W. Jay Ramsey,
Linda Muul,
Richard A. Morgan,
W. French Anderson (4)
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.
R. M. Blaese, C. A. Mullen, W. J. Ramsey, National Center for
Human Genome Research, National Institutes of Health (NIH), Building
49, Room 2A03, Bethesda, MD 20892, USA, and National Cancer Institute
(NCI), NIH, Bethesda, MD 20892, USA.
K. W. Culver, M. Clerici, G. Shearer, J. J. Greenblatt, S. A.
Rosenberg, NCI, NIH, Bethesda, MD 20892, USA.
A. D. Miller, Fred Hutchinson Cancer Research Center, Seattle, WA
98104, USA.
C. S. Carter, T. Fleisher, H. Klein, Clinical Center, NIH, Bethesda, MD
20892, USA.
L. Chang and W. F. Anderson, National Heart, Lung, and Blood Institute
(NHLBI), NIH, Bethesda, MD 20892, USA.
Y. Chiang and P. Tolstoshev, Genetic Therapy, Gaithersburg, MD 20878,
USA.
M. Berger, Department of Pediatrics, Case Western Reserve University
School of Medicine, Cleveland, OH 44106, USA.
L. Muul, National Center for Human Genome Research, NIH, Bethesda, MD
20892, USA.
R. A. Morgan, National Center for Human Genome Research, NIH, Bethesda,
MD 20892, USA, and NHLBI, NIH, Bethesda, MD 20892, USA.
(1) To whom correspondence should be addressed at the National Center
for Human Genome Research. E-mail:mblaese{at}nchgr.nih.gov
(2) Present address: Cattedra Di Immunogia, Universita Milano,
Milan 20133, Italy.
(3) Present address: Division of Pediatrics, M. D. Anderson
Cancer Center, Houston, TX 77030, USA.
(4) Present address: Norris Cancer Center, University of Southern
California School of Medicine, Los Angeles, CA 90033, USA.
