突变Ki-ras基因修饰的肺癌DC疫苗的体外抗癌活性 |
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引用本文: | 喻璟瑞,陆燕蓉,朱文,王艳萍,陈小禾,易成,罗德云,Michael T.Lotze,周清华. 突变Ki-ras基因修饰的肺癌DC疫苗的体外抗癌活性[J]. 中国肺癌杂志, 2004, 7(2): 104-107 |
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作者姓名: | 喻璟瑞 陆燕蓉 朱文 王艳萍 陈小禾 易成 罗德云 Michael T.Lotze 周清华 |
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作者单位: | 1. 610041,成都,四川大学华西医院四川省肺癌分子重点实验室、肿瘤中心 2. 15260 美国宾夕法尼亚州,匹兹堡大学肿瘤中心肿瘤外科 |
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基金项目: | 国家自然科学基金 (No .30 0 0 0 2 0 6),高等学校博士点基金(No .2 0 0 0 55)资助~~ |
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摘 要: | 目的 探讨以Ki-ras基因12位密码子点突变为靶点,构建DC-Ad-Ki-ras(V12)肺癌疫苗及其抗肺癌免疫治疗的可能性。方法 应用重组腺病毒的方法将人Ki-ras基因12位密码子点突变(由甘氨酸转变为缬氨酸)的cDNA导入DC,构建DC-Ad—Ki-ras(V12)肺癌疫苗,以流式细胞术、PCR、MLR和CTL等方法检测其免疫活性。结果 (1)DC-Ad-Ki-ras(V12)肺癌疫苗小仅能表达人Ki—ras(V12)基因,且能明显刺激T细胞增殖及提高CTL的杀伤作用。(2)突变Ki-ras基因修饰的DC免疫小鼠后,可产生针对表达Ki—ras(V12)基因的Lewis肺癌的特异件杀伤作用,但对B16黑色素瘤细胞则无明显杀伤作用。结论 以人突变Ki—ras基因修饰的肺癌DC疫苗可在体外特异性诱导抗可表达Ki-ras(V12)基因的Lewis肺癌的活性。
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关 键 词: | 基因突变 Ki-ras基因 基因修饰 肺癌 DC 疫苗 抗癌活性 树突状细胞 |
修稿时间: | 2004-02-13 |
Anti-tumor activities of lung cancer dendritic cell vaccine modified by mutant Ki-ras gene in vitro |
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Abstract: | Objective To construct a DC-Ad-Ki-ras(V12) vaccine and investigate the anti-tumor activities of lung cancer dendritic cell vaccine modified by mutant Ki-ras gene in vitro. Methods Ki-ras(V12) cDNA was transfected into cultured bone marrow-derived DC with the recombinant adenovirus [(Ad-Ki-ras(V12)] containing human mutant Ki-ras gene. Anti-tumor activity of the vaccine was studied in vitro by flow cytometry, PCR, MLR and cytotoxicity assay. Results (1) The DC vaccine was confirmed not only to express Ki-ras(V12) gene, but also to remarkably stimulate lymphocyte proliferation and improve CTL activity. (2) The DC vaccine modified by mutant Ki-ras gene could induce specifical CTL activity of immunized mice against Lewis lung carcinoma that could express Ki-ras(V12) gene, but not to B16. Conclusion The DC vaccine modified by mutant Ki-ras gene can induce obvious anti-tumor activities against Lewis lung carcinoma that can express Ki-ras(V12) gene. |
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Keywords: | Lung neoplasms Dendritic cell Mutant Ki-ras gene DNA vaccine |
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