B. Garciahernandez et I. Sanchezgarcia, RETROVIRAL VECTOR DESIGN FOR GENE-THERAPY OF CANCER - SPECIFIC-INHIBITION AND TAGGING OF BCR-ABL(P190) CELLS, Molecular medicine, 2(1), 1996, pp. 125-133
Citations number
26
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Cell Biology
Background: The main difficulty in providing effective treatment of pa
tients with cancer is distinguishing between tumor and normal cells. T
he chimeric molecules created by cancer-associated chromosomal abnorma
lities (such as the BCR-ABL fusion protein) represent ideal therapeuti
c targets since they are unique to the disease slate. A major challeng
e, however, is how to deliver the specific anti-tumor agent into every
tumor cell. Material and Methods: In this report we describe the use
of a novel strategy to introduce specific anti-tumor reagents into eve
ry tumor cell. It uses retroviral vectors encoding both antisense tran
scripts specific for the BCR-ABL(p190) fusion junction (the specific a
nti-tumor drug) and a truncated human CD5 cDNA, which allows selection
of the infected cells. In order to coexpress the anti-sense molecule
with the truncated human CD5 gene, the picornavirus internal ribosome-
entry site was incorporated in the constructs. Results: When the antis
ense transcripts in the CD5-retroviral vector were introduced into Ba/
F3+p190 cells rendered interleukin 3 (IL-3) independent by expression
of the BCR-ABL sequences, the cells died upon IL-3 withdrawal, as meas
ured by the absence of CDS-positive cells. Control Ba/F3+p210 cells in
fected with the same virus did not die in the absence of IL-3. Conclus
ions: These data suggest a novel strategy for cancer treatment which i
ncorporates the use of a retrovirus coexpressing both a selectable sur
face marker and a tumor-specific agent.