Anti-tumor immunity elicited by direct intratumoral administration of a recombinant adenovirus expressing either IL-28A/IFN-λ2 or IL-29/IFN-λ1

Interleukin (IL)-28A/inteiferon (IFN)-lambda 2 and IL-29/IFN-lambda 1 have been demonstrated to elicit direct and indirect anti-tumor actions. In this study, We constructed an adenovirus vector expressing either IL-28A/IFN-lambda 2 (AdIL-28A) or IL-29/IFN-lambda 1 (AdIL-29) to evaluate the therapeutic properties of intraturnoral injection of recombinant adenovirus to apply for the clinical implementation of cancer gene therapy. Despite the lack of an anti-proliferative effect on MCA205 and B16-F10 cells, a retarded growth of established subcutaneous tumors was observed following multiple injections Of either AdIL-28A or AdIL-429 when compared with AdNull. In vivo cell depletion experiments displayed that both NK cells and CD8(+) T cells have a major role in AdIL-28A-mediated tumor growth suppression. A significant increase in the number of infiltrating CD8(+) T cells into the tumors-treated with either AdIL-28A or AdIL-29 was observed. Moreover, specific ant-Rumor cytotoxic T lymphocyte reactivity was detected in spleen cells from animals treated with either AdIL-28A or AdIL-29. In IFN-gamma-deficient mice, anti-tumor activities of AdIL-28A were completely impaired, indicating that IFN-gamma is critically involved in the tumor growth inhibition triggered by AdIL-28A. IL-12 provided a synergiostic anti-tumor effect when combined with AdIL-28A. These results indicate that AdIL-28A and AdIL-29 could be successfully utilized as an alternative cancer immunogene therapy.