Potential for Interferon-α-Based Therapy in Mesothelioma: Assessment in a Murine Model

Abstract

Malignant mesothelioma is an aggressive tumor, usually induced by asbestos exposure, that has a poor prognosis and is unresponsive to conventional therapy. The present study was aimed at assessing the potential for interferon-α (IFN-α)-based therapies in a murine model for malignant mesothelioma. The effect of recombinant human IFN-α B/D on tumor growth, alone and in combination with either of two immunomodulatory and antiproliferative agents β-carotene or α-difluoromethylornithine (DFMO), was assessed. The data suggest that IFN-α treatment is most efficacious when commenced early in tumor development. Combination of IFN-α with either DFMO or dietary β-carotene supplementation improved the effect of an otherwise suboptimal IFN-α therapy regimen. Both IFN-α and α-carotene had in vivo stimulatory effects on immune cells, perhaps indirectly by inhibiting TGF-β generation. The immunomodulatory effects may contribute, at least in part, to the positive antitumor and clinical activities of the treatments in this model.