Retroviral coexpression of IFN-alpha and IFN-gamma genes and inhibitory effects in chronic myeloid leukemia cells.
Interferon (IFN) is an effective treatment for chronic myeloid leukemia (CML) in chronic phases, and a number of in vitro antileukemic effects of IFN on CML cells have been reported. The transfer of cytokine genes into tumor cells is reportedly a valuable approach to improve the antitumor activity of cytokines in various models. We first investigated the possibility of transducing CML cells with the retroviral vectors LIalpha2SN and LIgammaSN, encoding the IFN-alpha2 and IFN-gamma genes, respectively, and with the bicistronic vector LIalpha2IrIgammaSN coexpressing the IFN-alpha2 and IFN-gamma genes. We then analyzed the effects of IFN-alpha2 and IFN-gamma produced alone or simultaneously on the proliferation of CML cells. We optimized the transduction efficiency by using the CML-derived K562 cell line. We then introduced IFN genes into CML CD34+ cells. Secretion of IFN-alpha and IFN-gamma was demonstrated in K562 and CML CD34+ cells transduced with the different vectors. The MHC class I antigens were overexpressed in both K562 and CML CD34+ transduced cells. Inhibition of the proliferation of LIalpha2IrIgammaSN-transduced CML cells was greater than with the LIalpha2SN and the LIgammaSN-transduced CML cells. We demonstrate an additive effect of IFN-alpha and IFN-gamma on the inhibition of K562 and CML CD34+ cell proliferation.
Salesse
S
S
Laboratoire de Greffe de Moelle, UMR CNRS 5540, Fédération de Recherche 60 Biologie des Greffes, Université Victor Segalen Bordeaux, France.
Lagarde
V
V
Ged
C
C
de Verneuil
H
H
Reiffers
J
J
Mahon
F X
FX
D018952:Antigens, CD34 / Q000378:metabolism; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D014410:Tumor Stem Cell Assay
D018952:Antigens, CD34; D017931:DNA Primers; D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma