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

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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-hlL-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-y),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.
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