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A novel herpes vector for the high-efficiency transduction of normal and
malignant human hematopoietic cells
D Dilloo, D Rill, C Entwistle, M Boursnell, W Zhong, W Holden, M Holladay, S Inglis and M Brenner
Cell and Gene Therapy Program, St Jude Children's Research Hospital,
Memphis, TN 38105, USA.
Herpes simplex viruses (HSVs) would offer numerous advantages as vectors
for gene transfer, but as yet they have not proved capable of transducing
hematopoietic cells. Using a genetically inactivated form of HSV that is
restricted to a single cycle of replication (disabled single-cycle virus,
[DISC-HSV]), we have transduced normal human hematopoietic progenitor cells
and primary leukemia blasts with efficiencies ranging from 80% to 100%, in
the absence of growth factors or stromal support. Toxicity was low, with
70% to 100% of cells surviving the transduction process. Peak expression of
transferred genes occurred at 24 to 48 hours after transduction with the
DISC-HSV vector, declining to near background levels by 14 days. Despite
this limitation, sufficient protein is produced by the inserted gene to
permit consideration of the vector for applications in which transient
expression is adequate. One example is the transfer of immunostimulatory
genes, to generate leukemia immunogens. Thus, murine A20 leukemia cells
transduced with a DISC-HSV vector encoding granulocyte-macrophage
colony-stimulating factor were able to stimulate a potent antitumor
response in mice, even against pre-existing leukemia. The exceptional
transducing ability of the DISC-HSV vector should therefore facilitate
genetic manipulation of normal and malignant human hematopoietic cells for
biological and clinical investigation.
Volume 89,
Issue 1,
pp. 119-127,
01/01/1997
Copyright © 1997 by The American Society of Hematology
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