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Construction and anti-tumor effects of recombinant fowlpox virus expressing Newcastle disease virus hemagglutinin-neuramidinase gene
引用本文:LI Xiao JIN Ningyi LIAN Hai GUAN Goufang SUN Lili LI Xue mei ZHENG Hongling. Construction and anti-tumor effects of recombinant fowlpox virus expressing Newcastle disease virus hemagglutinin-neuramidinase gene[J]. 科学通报(英文版), 2006, 51(22): 2724-2730. DOI: 10.1007/s11434-006-2176-z
作者姓名:LI Xiao JIN Ningyi LIAN Hai GUAN Goufang SUN Lili LI Xue mei ZHENG Hongling
作者单位:[1]Genetic Engineering Laboratory of PLA, The Eleventh Institute ofAcademy of Military Medical Sciences of PLA, Changchun 130062,China [2]Faculty of Agriculture Sciences of Jilin University, Changchun 130062,China [3]The Second Hospital, Bethune Faculty of Medical Sciences of JilinUniversity, Changchun 130041, China
基金项目:This work was supported by the major research plan of National Natural Science Foundation of China (Grant No. 39893290-4-3).
摘    要:Hemagglutinin-neuramidinase (HN), a Newcastle disease virus-derived protein, not only mediates receptor recognition but also possesses neuraminidase (NA) activity, the ability to cleave a component of those receptors, N-acetylneuraminic acid (NAcneu, sialic acid). It is known that this protein in mammalian species, including human beings, has interesting anti-neoplastic as well as immune stimulating properties. To explore the use of the HN gene in cancer gene therapy, we constructed a recombi-nant fowlpox virus expressing the HN protein (vFV-HN) and compared the anti-tumor activity of the recombinant virus with that of wild-type fowlpox virus (FPV) in vivo and in vitro. Here we found that although B16 cells were somewhat resistant to the basal cytotoxic effect of wild-type fowlpox virus, infection with vFV-HN caused a pronounced cytotoxic effect and, the survival of tumor-bearing mice immunized with vFV-HN was significantly increased compared with the survival of mice immunized with the FPV alone. Furthermore, the immunization of mice with vFV-HN elicited a B16 tumor-specific cytotoxic T lymphocyte (CTL) response and clonal expansion of both CD4 and CD8 T cell populations in vivo. In addition, T cells from lymph nodes of mice vaccinated with vFV-HN secreted high levels of the Th1 cytokine IL-2 and IFN-γ, indicating that the regression of tumor cells is related to a Th1-type dominant immune response. These results demonstrate that vaccination with vFV-HN may be a potential strategy for cancer gene therapy.

关 键 词:NDV HN基因 抗肿瘤 蛋白质 受体识别
收稿时间:2006-05-29
修稿时间:2006-05-292006-08-15

Construction and anti-tumor effects of recombinant fowlpox virus expressing Newcastle disease virus hemagglutinin-neuramidinase gene
Xiao Li,Ningyi Jin,Hai Lian,Goufang Guan,Lili Sun,Xuemei Li,Hongling Zheng. Construction and anti-tumor effects of recombinant fowlpox virus expressing Newcastle disease virus hemagglutinin-neuramidinase gene[J]. Chinese science bulletin, 2006, 51(22): 2724-2730. DOI: 10.1007/s11434-006-2176-z
Authors:Xiao Li  Ningyi Jin  Hai Lian  Goufang Guan  Lili Sun  Xuemei Li  Hongling Zheng
Affiliation:(1) Genetic Engineering Laboratory of PLA, The Eleventh Institute of Academy of Military Medical Sciences of PLA, Changchun, 130062, China;(2) Faculty of Agriculture Sciences of Jilin University, Changchun, 130062, China;(3) The Second Hospital, Bethune Faculty of Medical Sciences of Jilin University, Changchun, 130041, China
Abstract:Hemagglutinin-neuramidinase (HN), a Newcastle disease virus-derived protein, not only mediates receptor recognition but also possesses neuraminidase (NA) activity, the ability to cleave a component of those receptors, N-acetylneuraminic acid (NAcneu, sialic acid). It is known that this protein in mammalian species, including human beings, has interesting anti-neoplastic as well as immune stimulating properties. To explore the use of the HN gene in cancer gene therapy, we constructed a recombinant fowlpox virus expressing the HN protein (vFV-HN) and compared the anti-tumor activity of the recombinant virus with that of wild-type fowlpox virus (FPV) in vivo and in vitro. Here we found that although B16 cells were somewhat resistant to the basal cytotoxic effect of wild-type fowlpox virus, infection with vFV-HN caused a pronounced cytotoxic effect and, the survival of tumor-bearing mice immunized with vFV-HN was significantly increased compared with the survival of mice immunized with the FPV alone. Furthermore, the immunization of mice with vFV-HN elicited a B16 tumor-specific cytotoxic T lymphocyte (CTL) response and clonal expansion of both CD4+ and CD8+ T cell populations in vivo. In addition, T cells from lymph nodes of mice vaccinated with vFV-HN secreted high levels of the Th1 cytokine IL-2 and IFN-γ, indicating that the regression of tumor cells is related to a Th1-type dominant immune response. These results demonstrate that vaccination with vFV-HN may be a potential strategy for cancer gene therapy.
Keywords:NDV   HN gene   fowlpox virus vector   anti-tumor.
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