Retroviral vector-mediated transfer of the interferon-alpha gene in chronic myeloid leukemia cells

The transfer and expression of cytokine genes into tumor cells is reportedl y a valuable approach to improve the antitumor activity of cytokines in var ious models. Interferon (IFN)-alpha may induce hematological remission in c hronic myeloid leukemia (CML) patients, but only a small proportion of pati ents achieve a sustained, complete cytogenetic remission. We have investiga ted the possibility of transducing CML cells with the retroviral vector LI alpha(2)SN, which encodes the IFN-alpha 2 gene. We first optimized the tran sduction efficiency using the CML-derived K562 cell line. A transduction ef ficiency of 50% and 85% after three and six infections, respectively, was o btained in K562 cells. We then expressed IFN-alpha 2 in CML cells by transd ucing the latter with LI alpha(2)SN viral particles. The IFN-alpha secretio n after three and six infections was 5,400 and 18,000 U/24 hours/10(6) cell s for unselected K562 cells and 7,000 and 290 U/24 hours/10(6) cells for CM L CD34(+) cells at days 4 and 5. Moreover, the major histocompatibility com plex class I antigens were overexpressed after infection with LI alpha(2)SN in both K562 and CML CD34(+) cells. The proliferation tin liquid culture) and the cloning efficiency of these CML cells were significantly decreased after LI alpha(2)SN treatment. By contrast, the proliferation of cord blood CD34(+) cells was not affected by transduction with LI alpha(2)SN. These r esults demonstrate the transduction efficiency of CML cells and suggest the possibility of CML cell immunotherapy with retroviral gene transfer of dif ferent cytokines such as IFN-alpha.