X-linked severe combined immunodeficiency (SCID-X1) is a recessive heredita
ry disorder in which early T and Natural Killer (NK) lymphocyte development
is blocked. The genetic disorder results from mutations in the common gamm
ac chain that participates in several cytokine receptors including the inte
rleukin-2 (II-2), II-4, II-7, II-9 II-15 receptors. SCID-XI offers a reliab
le model for gene therapy as it is a lethal condition that is, in many case
s, curable by allogeneic bone marrow transplantation. We have shown that re
trovirus-mediated transfer of the gammac cDNA induced gammac chain expressi
on and restored the function of the high-affinity IL-2 receptor on SCI-XI E
BV-transformed B-cell lines. We have the designed culture conditions to stu
dy NK-cell and T-cell development of CD34+ hematopoietic progenitor cells.
in the culture systems, gammac transduced CD34+ marrow cells from two SCID-
XI patients were able to mature into CD56+ and/or CD16+ NK cells and into C
D4+ TCR alpha beta+ T cells. These preclinical results set the basis for a
clinical study of ex-vivo gammac gene transfer into CD34+ cells from SCID-X
I patients. (C) 2001 Editions scientifiques et medicales Elsevier SAS.