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

作　　者：HUANG Hai-yan MENG Xiang-wei LI Xiao SUN Li-li KAN Shi-fu LIU Lei PIAO Bing-guo YANG Guo-hua WANG Zhuo-yue WANG Yu-hang QI Yan-xin JIN Ning-yi 

机构地区：[1]Department of Gastroenterology, the First Hospital of Jilin University, Changchun 130021, P. R. China [2]Laboratory of Genetic Engineering of PLA, Military Veterinary Institute, Academy of Military Medical Sciences, Changchun 130062, P. R. China [3]Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Institute, Academy of Military Medical Sciences, Changchun 130062, P. R. China [4]Department of Head and Neck Surgery, Tumor Hospital of Jilin Province, Changchun 130012, P. R. China [5]Digestive lnternal Medicine, Xuzhou Center Hospital, Xuzhou 221009, P. R. China

出　　处：《Chemical Research in Chinese Universities》2011年第5期836-840,共5页高等学校化学研究（英文版）

基　　金：Supported by the Genetically Modified Organisms Breeding Major Projects, China(No.2009ZX08006-002B);the Key Technologies Research and Development Program of Jilin Province, China(No.10ZDGG007);the Postdoctoral Science Foundation Funded Project of China(No.20100481057)

摘　　要：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.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.

关 键 词：Newcastle disease virus Human interleukin 18（hlL-18） Hemagglutinin-neuraminidase（HN） HEPATOMA Antitumor immunity 

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