Adenovirus-Mediated Murine Interferon-γ Receptor Transfer Enhances the Efficacy of IFN-γ in Vivo

Abstract

Interferon γ (IFN-γ) plays an important role in immune response, apoptosis, and anti-tumor activity. Its biological activity depends on expression of IFN-γ receptor (IFN-γR). To address whether increased expression of IFN-γR is associated in vivo with a higher biological response by IFN-γ, we constructed an adenovirus vector including murine IFN-γR (Ad-mIFN-γR). We confirmed the appropriate function of mIFN-γR derived from Ad-mIFN-γR based on the observation of signal transduction and transcription. We also found that elevated expression of mIFN-γR increases sensitivity to recombinant murine IFN-γ (rmIFN-γ) in vitro in target cells. Furthermore, we demonstrated that the growth rate of tumors transfected with Ad-mIFN-γR is suppressed in response to rmIFN-γ in vivo and that such growth suppression is partly due to apoptosis. To our knowledge, this is the first report of adenovirus-mediated IFN-γR gene transfer being effective in augmenting the biological activity of IFN-γ, and the strategy employed in the present study will be useful in studying other kinds of cytokine receptors and applications to gene therapy for cancer and infectious diseases.