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腺病毒介导的白介素12对恶性脑肿瘤的基因治疗

Adenovirus-mediated interleukin-12 gene therapy for malignant brain tumor

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【作者】 刘云会薛一雪程鹏欧少武藏培卓杨国瑞

【Author】 LIU Yun hui, XUE Yi xue, CHENG Peng, et al. (Department of Neurosurgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China)

【机构】 中国医科大学附属第一医院神经外科!辽宁沈阳110001中国医科大学基础医学院神经生物学教研室!辽宁沈阳110001中国医科?

【摘要】 目的 构建表达鼠白介素 1 2 ( IL-1 2 )基因的重组腺病毒 ( Ad/ IL-1 2 ) ,并测试对小鼠 GL-2 6脑胶质瘤的实验治疗。方法 将 IL-1 2的 P3 5 和 P40 的两个亚单位基因分别插入腺病毒的 E1和 E3区 ,构建 Ad/ IL-1 2。结果 肿瘤内注射 Ad/ IL-1 2显著地延长了动物的生存时间 ,有 3 0 %的动物生存期超过了 6个月。离体脾脏细胞CTL分析没有检测出 T淋巴细胞溶解活性 ,而从肿瘤内收集的 T淋巴细胞却有强烈的杀伤活性。结论 局部表达IL-1 2是一个很有潜力的治疗脑胶质瘤的手段 ,这种治疗效果源于肿瘤特异性克隆 T淋巴细胞的肿瘤内浸润。

【Abstract】 Objective A recombinant adenovirus expressing the murine interleukin 12 (IL 12) was constructed and tested in the mice GL 26 brain tumor model.Methods P 35 and P 40 cDNA were inserted to the E1 and E3 region of Ad5 genomic DNA, respectively. Recombinant Adenovirus were rescued and propagated using the 293 cell line.Results Intratumoral administration of this cytokine vector increased significantly survival time of the animals with 30% of the treated animals still living over 6 months. No significant cytolytic activity was detectable using classical cytotoxicity assays from in vitro restimulated splenocytes. CTL assay for tumor infiltrate T cell shown significant cytolytic activity. Mice which rejected GL 26 and were tumor free for 3 months resisted a second challenge with GL 26 glioma cells.Conclusion These data indicate that local expression of IL 12 may also be an attractive treatment strategy for brain tumor that correlated to clonal tumor specific T cell expansions in the tumor.

【关键词】 脑肿瘤基因治疗腺病毒白介素12
【Key words】 GliomaGene therapyAdenovirusInterleukin 12
【基金】 国家自然科学基金资助课题 ( 3 0 0 70 768)
  • 【文献出处】 中风与神经疾病杂志 ,Journal of Apoplexy and Nervdus Diseases , 编辑部邮箱 ,2001年04期
  • 【分类号】R739.4
  • 【被引频次】2
  • 【下载频次】80
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