Retroviral Coexpression of IFN-α and IFN-γ Genes and Inhibitory Effects in Chronic Myeloid Leukemia Cells

Abstract

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 LIα2SN and LIγSN, encoding the IFN-α2 and IFN-γ genes, respectively, and with the bicistronic vector LIα2IrIγSN coexpressing the IFN-α 2 and IFN-γ genes. We then analyzed the effects of IFN-α2 and IFN-γ 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-α and IFN-γ 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 LIα2IrIγSN-transduced CML cells was greater than with the LI alpha 2SN and the LIγSN-transduced CML cells. We demonstrate an additive effect of IFN-α and IFN-γ on the inhibition of K562 and CML CD34⁺ cell proliferation.