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 (CM L) 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 o f cytokines in various models. We first investigated the possibility of tra nsducing CML cells with the retroviral vectors LI alpha 2SN and LI gamma SN , encoding the IFN-alpha 2 and IFN-gamma genes, respectively, and with the bicistronic vector LI alpha 2IrI gamma SN co-expressing the IFN-alpha 2 and IFN-gamma genes. We then analyzed the effects of IFN-alpha 2 and IFN-gamma produced alone or simultaneously on the proliferation of CML cells. We opt imized the transduction efficiency by using the CML-derived K562 cell line. We then introduced IFN genes into CML CD34(+) cells. Secretion of IFN-alph a and IFN-gamma was demonstrated in K562 and CML CD34(+) cells transduced w ith the different vectors. The MHC class I antigens were overexpressed in b oth K562 and CML CD34(+) transduced cells. Inhibition of the proliferation of LI alpha 2IrI gamma SN-transduced CML cells was greater than with the LI alpha 2SN and the LI gamma SN-transduced CML cells. We demonstrate an addi tive effect of IFN-alpha and IFN-gamma on the inhibition of K562 and CML CD 34(+) cell proliferation.