Human and mouse IFN-beta gene therapy exhibits different anti-tumor mechanisms in mouse models

Previously, we suggested that local human interferon-beta (IFN-beta) gene t herapy with replication-defective adenoviral vectors can be an effective ca ncer treatment. Clinical trials to treat cancers with adenovirus expressing the human IFN-beta gene (IFNB1) has been planned. As a continued effort to explore the mechanisms of action of human IFN-beta gene therapy that can o ccur in the clinical setting, we tested mouse IFN-beta gene therapy in huma n xenograft tumors in both ex vivo and in vivo models. Delivery of the mous e IFN-beta gene (Ifnb) caused tumor inhibition; this effect was dependent o n the indirect anti-tumor activities of IFN-beta, notably a stimulation of natural killer cells. IFN-beta does not show cross-species activity in its anti-proliferative effect and mouse IFN-beta does not cause as significant an anti-proliferative effect on mouse tumor cells as human IFN-beta causes on human tumor cells. Therefore, we believe that mouse models using either human IFN-beta or mouse IFN-beta gene transfer do not capture all aspects o f the action of adenovirus-mediated human IFN-beta gene therapy that may be present in the clinical setting. Due to its multiple mechanisms of action, human IFN-beta gene therapy may be effective in treating human cancers tha t are either sensitive or resistant to the direct anti-proliferative effect of IFN-beta.