Transplantation of transduced nonhuman primate CD34(+) cells using a gibbon ape leukemia virus vector: restricted expression of the gibbon ape leukemia virus receptor to a subset of CD34(+) cells
Ba. Bunnell et al., Transplantation of transduced nonhuman primate CD34(+) cells using a gibbon ape leukemia virus vector: restricted expression of the gibbon ape leukemia virus receptor to a subset of CD34(+) cells, GENE THER, 6(1), 1999, pp. 48-56
The transduction efficiencies of immunoselected rhesus macaque (Macaca mula
tta) CD34(+) cells and colony-forming progenitor cells based on polymerase
chain reaction (PCR) analysis were comparable for an amphotropic Moloney mu
rine leukemia virus (MLV) retroviral vector and a retroviral vector derived
from the gibbon ape leukemia virus (GaLV) packaging cell line, PG13. On pe
rforming autologous transplantation studies using immunoselected CD34(+) ce
lls transduced with the GaLV envelope (env) retroviral vector, less than 1%
of peripheral blood (PB) contained provirus. This was true whether bone ma
rrow (BM) or cytokine-mobilized PB immunoselected CD34(+) cells were reinfu
sed. This level of marking was evident in two animals whose platelet counts
never fell below 50 000/mu l and whose leukocyte counts had recovered by d
ays 8 and 10 after having received 1.7 x 10(7) or greater of cytokine-mobil
ized CD34(+) PB cells/kg. Reverse transcriptase(RT)PCR analysis of CD34(+)
subsets for both the GaLV and amphotropic receptor were performed. The expr
ession of the GaLV receptor was determined to be restricted to CD34(+) Thy-
1(+) cells, and both CD34(+) CD38(+) and CD34(+) CD38dim cells, while the a
mphotropic receptor was present on all CD34(+) cell subsets examined. Our f
indings suggest that, in rhesus macaques, PG13-derived retroviral vectors m
ay only be able to transduce a subset of CD34(+) cells as only CD34(+) Thy-
1(+) cells express the GaLV receptor.