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转染肝癌总RNA的树突状细胞疫苗对肝癌的抑制作用及其机制
The suppression of tumor growth of hepatocellular carcinoma induced by dendritic cell vaccine transfected with tumor cell total RNA
【摘要】 目的探讨转染肝癌细胞总RNA转染的树突状细胞(DC)疫苗抑制肝癌作用及其机制。方法采用粒/巨噬细胞集落刺激因子(GM-CSF)和白细胞介素(IL)-4联合培养6 d成小鼠骨髓来源不成熟DC(iDC),质脂体转染肝癌细胞系Hepa1-6 RNA入iDC,用LPS刺激后成为Hepal-6 RNA/DC疫苗,对照组为iDC组、LPS/DC组Saline组,以每只2×106个细胞腹腔注射免疫小鼠每周1次共3次,然后接种5×105 Hepal-6细胞,观察肿瘤生长情况、特异性CTL活性的测定以及抗体阻断实验。结果实验组Hepal-6 RNA/DC组肿瘤在第8周为(8.5±3.6)mm,而iDC组、LPS/ DC组、Saline对照组分别为(36.6±3.6)、(31.3±4.7)、(32.2±4.0)mm,与实验组比较差异均有统计学意义(P<0.05)。实验组脾细胞对Hepal-6细胞有特异性杀伤效应,而对肺癌LLC细胞无杀伤活性。所诱导的抗肿瘤效应细胞包括CD8+、CD4+T淋巴细胞。结论肝癌细胞的总RNA转染的DC肿瘤疫苗能诱导CD8+、CD4+T细胞免疫,是较有临床应用前景的肝癌免疫治疗方法。
【Abstract】 Objective To induce efficient and specific suppression of tumor growth of hepatocellu- lar carcinoma(HCC)induced by dendritic cell vaccine transfected with tumor cell total RNA.Methods DC isolated from mice marrow were incubated with recombinant mouse granulocyte macrophage colony- stimulationg factor(10μg/L)and mouse IL-4(500 U/ml)for 6 days,which called immature DC (iDC),and transfected with Hepal-6 RNA and stimulated with LPS.The Hepal-6 RNA/DC vaccines (2×10~6)were injected intraperotoneally weekly for 3 times,then 5×10~5 Hepal-6 cells or iDC,LPS/DC were inoculated.The tumor growth and antitumor efficacy of CTL were measured.Result The tumor size in Hepal-6 RNA/DC vaccine group was(8.5±3.6)ram.The tumor size in iDC group,LPS/DC group and saline group was(36.6±3.6),(31.3±4.7 )and(32.2±4.0)mm,respectively,which was significantly different from that in Hepal-6 RNA/DC vaccine group(P<0.05).The spleen ceils in Hep- al-6 RNA/DC vaccine group could specifically kill the Hepal-6 cells but not for LLC cells.The anticancer effectors were CD8~+ and CD4~+ T cells.Conclusion DC transfected by HCC-derived total RNA could in- duce specific anti-tumor immune response both from CD8~+ and CD4~+ T cells.
【Key words】 Dendritic cells; Carcinoma,hepatocellular; Vaccine; Cytotoxic T lymphocyte;
- 【文献出处】 中华实验外科杂志 ,Chinese Journal of Experimental Surgery , 编辑部邮箱 ,2006年10期
- 【分类号】R735.7
- 【被引频次】6
- 【下载频次】191