基因工程肿瘤细胞融合疫苗诱导Th1应答抗肿瘤

目的　探讨基因工程肿瘤细胞融合疫苗的抗肿瘤作用。方法　将鼠源性IL 12 (mIL 12 )基因转染J5 5 8细胞制备工程瘤细胞 ,再与树突状细胞进行融合后免疫BALB c小鼠 ,14d后再以不同剂量的瘤细胞攻击小鼠以观察其保护效力。结果　制备的工程瘤细胞J5 5 8经测试其培养上清中mIL 12表达量为 (870± 6 0 )pg·(10 5细胞 ) - 1 ·ml- 1 ;与树突状细胞体外融合后 ,镜下测得细胞融合率约为 30 % ;收集免疫小鼠腹股沟及月国窝淋巴结细胞与肿瘤细胞共培养 ,其上清IFN γ含量较对照组高 ;体内、外特异性抗肿瘤实验均显示该型瘤苗具有良好的抗瘤作用。结论　免疫小鼠体内诱导Th1应答 ,其明显的抗肿瘤功效为临床应用提供了可能性

Induction of Th1 immune response against tmnor by genetically engineered fusion of tumnor cells and dendritic cells

OBJECTIVE: To study the antitumor activity of engineered fusion of tumor cell and dendritic cells (DC). METHODS: J558 tumor cells were transfected with mouse IL-12 (mIL-12) gene and then fused with DCs to develop a hybrid-engineered tumor vaccine. BALB/c mice were challenged with wild-type J558 tumor cells 14 days after vaccinated with hybrid-engineered J558. RESULTS: mIL-12 was detected at (870 +/- 60) pg.(10(5) cells)(-1).ml(-1) in the culture supernatants and the cell-fusion rate was about 30% by co-focal microscopy. In addition, the lymphocytes from popliteal nodes and groin nodes of these mice vaccinated with hybrid-engineered J558 secreted higher levels of IFN-gamma than that of other control mice, and vaccination of mice with the fusion vaccine induced more efficient tumor-specific CTL cytotoxicity against wild-type tumor cells in vitro and with efficient antitumor immunity in vivo. CONCLUSION: It suggested that vaccination of mice with the fusion vaccine induced stronger Th1-dominant responses and this approach could perhaps be applied to clinical settings of DCs-based cancer vaccines.