Pegylated and conventional interferon-α induce comparable transcriptional responses and inhibition of tumor growth in a human melanoma SCID mouse xenotransplantation model

Abstract

Interferon-alpha (IFM-α) is widely used for the treatment of viral infections and primary cancers. In the present study, we investigated whether the anti-proliferative activity of IFN-α is capable of inhibiting melanoma tumor development in the absence of protective immune responses in a severe combined immunodeficiency (SCID) mouse model. Mice treated with either regular (100 μg/ 3 times per week) or pegylated (300 μg/once weekly) human IFN-α 2a showed a marked reduction in tumor weight after 4 wk of treatment. Tumor weight in pegylated and conventional IFN-α-treated animals was reduced by 61% and 67%, respectively, as compared to saline control (both P≤0,01). A decrease of proliferation and an increase of apoptotic tumor cells were observed in IFN-treated tumors. DNA microarrays were applied to analyse transcriptional responses in tumors after 4 wk of treatment and a subset of about 90 genes was differentially expressed. Twenty-four novel and five known interferon-inducible genes were up- and 65 genes downregulated. A direct comparison of IFN-α and pegylated IFN-α did not reveal any significant differences in tumor growth inhibition indicating that this novel and more stable class of IFN is functionally equivalent. Despite the structural difference between pegylated and conventional IFN-α, both agents caused similar transcriptional responses in human melanoma xenotransplants.