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

作　　者：赵海专[1] 陈祖兵[1] 陶剑平[2] 胡文杰[3] 喻瓴[4] 沈世强[1] 

机构地区：[1]武汉大学人民医院肝胆外科,430060 [2]中山大学中山医学院微生物教研室 [3]中山大学附属第一医院肝胆外科 [4]中山大学眼科中心

出　　处：《中华实验外科杂志》2006年第10期1200-1202,共3页Chinese Journal of Experimental Surgery

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2×10~6个细胞腹腔注射免疫小鼠每周1次共3次,然后接种5×10~5 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CD^(8+)、CD^(4+)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CD^(8+)、CD^(4+)T细胞免疫,是较有临床应用前景的肝癌免疫治疗方法。Objective To induce efficient and specific suppression of tumor growth of hepatocellular 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 colonystimulationg factor （10 μg/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） mm. 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 cells in Hepal-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 induce specific anti-tumor immune response both from CD8 ^＋ and CD4^＋ T cells.

关 键 词：树突状细胞 癌 肝细胞 疫苗 细胞毒T淋巴细胞 

分 类 号：R735.7[医药卫生—肿瘤]