CD4 + T Helper Cell-Independent Antitumor Response Mediated by Murine IFN- β Gene Delivery in Immunocompetent Mice

Abstract

Previously, we provided evidence that adenovirus-mediated interferon-β (IFN-β) gene therapy inhibits tumor formation and causes dramatic regression of established tumors in immunodeficient mice. We suggested that local IFN-β gene therapy with adenoviral vectors could be an effective treatment for cancer. In this report, the actions of murine IFN-β (MuIFN-β) gene delivery on both subcutaneous and metastatic tumors were evaluated in syngeneic immunocompetent mice. We found that the antitumor response mediated by MuIFN-β gene delivery relied on CD8⁺ T cells but was completely independent of CD4⁺ T cells. In fact, depletion of CD4⁺ T cells appeared to enhance the effect on tumor inhibition and animal survival induced by adenovirus-MuIFN-β gene delivery. Therefore, adenovirus-MuIFN-β gene therapy can bypass CD4⁺ T helper (Th) cells and activate an effective CD8⁺ T cell-dependent antitumor immunity in immunocompetent mice. Furthermore, we found that depletion of macrophages but not natural killer (NK) cells suppressed the antitumor response induced by MuIFN-β gene therapy. These data, together with our previous results, suggest that in the clinical setting, local adenovirus-mediated IFN-β gene therapy may lead to an efficient and long-lasting eradication of tumors by a direct antitumor effect and via activation of the innate and the adoptive immune systems.