Induction of Effective Antitumor Immune Response by Combined Administration of hIL-18 and NDV HN

To analyze the antitumor potential and mechanism of action of simultaneous Newcastle disease virus （NDV） hemagglutinin-neuraminidase（HN） and human interleukin 18（hIL-18） gene transfer in C57BL/6 mice with H22 hepatoma,the mouse model with H22 hepatoma was established in C57BL/6 mice, and the antitumor effects of the combined application of NDV HN and hIL-18 were evaluated in vivo. The results show that the growth of established tumors in mice immunized with adenovirus（Ad）-HN in conjunction with Ad-hIL-18 was significantly inhibited compared with that in mice immunized with Ad-HN, Ad-hIL-18 alone, or the empty vector（Ad-mock）. Furthermore, the immunization of mice with Ad-HN in conjunction with Ad-hIL-18 elicited strong natural killer activity and H22 tumor-specific cytotoxic T lymphocyte（CTL） responses in vivo. In addition, T cells from the lymph nodes of mice immunized with Ad-hIL-18 or Ad-HN＋Ad-hIL-18 secreted high levels of the Th1 cytokine IL-2 and interferon-γ （IFN-γ）, indicating that the regression of tumor cells is related to a Th1-type dominant immune response. These results demonstrate that vaccination with NDV HN together with hIL-18 may be a novel and powerful strategy for cancer immunotherapy.