Construction and anti-tumor effects of recombinant fowlpox virus expressing Newcastle disease virus hemagglutinin-neuramidinase gene  

作　　者：LI Xiao JIN Ningyi LIAN Hai GUAN Goufang SUN Lili LI Xue mei ZHENG Hongling 

机构地区：[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

出　　处：《Chinese Science Bulletin》2006年第22期2724-2730,共7页

基　　金：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 ) ，纽卡斯尔疾病导出病毒的蛋白质，不是仅仅调停受体识别而且拥有 neuraminidase (NA ) 活动，劈开那些受体的一个部件的能力， N-acetylneuraminic 酸(NAcneu， sialic ) 。包括人，在哺乳动物的种类的这蛋白质有有趣的反肿瘤以及有免疫力的刺激性质，这被知道。在癌症基因治疗探索 HN 基因的使用，我们构造了表示 HN 蛋白质(vFV-HN ) 的一个 recombinant 家禽痘病毒并且在 vivo 并且在 vitro 把 recombinant 病毒的 theanti 肿瘤活动与野类型的家禽痘病毒(FPV ) 的作比较。这里，我们发现尽管 B16 房间对野类型的家禽痘病毒的基础细胞毒素的效果有点抵抗，有 vFV-HN 的感染引起了显著细胞毒素的效果并且，与 vFV-HN 使免疫的忍受肿瘤的老鼠的幸存显著地与独自与 FPV 使免疫的老鼠的幸存相比被增加。而且，有 vFV-HNelicited 的老鼠的免疫 B16 肿瘤特定的细胞毒素的 T 淋巴细胞(CTL ) 回答和在 vivo 的 bothCD4+ 和 CD8+ T 房间人口的同种细胞的扩大。另外，从老鼠的淋巴节点的 T 房间种牛痘， Th1 cytokine IL-2 和 IFN-v 高级的 vFV-HN 藏匿了，显示肿瘤房间的回归与 Th1 类型主导的有免疫力的回答有关。这些结果证明有 vFV-HN 的种痘可以是为癌症基因治疗的潜在的策略。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 CDS＋ T cell populations in vivo. In addition, T cells from lymph nodes of mice vaccinated with vFV-HN secreted high levels of the Thl cytokineIL-2 and IFN-y, 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 

分 类 号：Q5[生物学—生物化学]