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

The Journal of Investigative Dermatology
Clemens KreplerHubert Pehamberger

Abstract

Interferon-alpha (IFN-alpha) 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-alpha 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 microg/3 times per week) or pegylated (300 microg/once weekly) human IFN-alpha 2a showed a marked reduction in tumor weight after 4 wk of treatment. Tumor weight in pegylated and conventional IFN-alpha-treated animals was reduced by 61% and 67%, respectively, as compared to saline control (both p< or =0.01). A decrease of proliferation and an increase of apoptotic tumor cells were observed in IFN-treated tumors. DNA microarrays were applied to analyze 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-alpha and pegylated IFN-alpha did not reveal any significant differences in tumor growth inhibition indicating that this novel and more stable class of IFN is...Continue Reading

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Citations

Dec 21, 2010·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Fredy SiegristUlrich Certa
Mar 14, 2016·Cancer Metastasis Reviews·J TímárE Rásó
Sep 7, 2006·Liver International : Official Journal of the International Association for the Study of the Liver·Hirohisa YanoMasamichi Kojiro
Apr 7, 2009·Experimental Dermatology·Carlo PincelliRiccardo G Borroni
Nov 12, 2016·Oncotarget·Nevenka Dudvarski StankovicMirko H H Schmidt
Jan 5, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stefano IndraccoloAlberto Amadori

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