Nakamura Motoyuki, Kikuchi Tetsuro, Kufe Donald W, Ohno Tsuneya
Department of Oncology, Institute of DNA Medicine, Jikei University, 3-25-8 Nishishinbashi, Minato-ku, 105-8461, Tokyo, Japan.
Cancer Immunol Immunother. 2004 Aug;53(8):690-6. doi: 10.1007/s00262-004-0511-2. Epub 2004 Mar 16.
Based on several previous studies indicating that transfection of genomic DNA can stably alter the character of the cells that take up the exogenous DNA, we investigated antitumor immunity conferred by fusions of syngeneic dendritic cells (DCs) and allogeneic fibroblasts (NIH3T3) transfected with genomic DNA from B16 tumor cells. Fusion cells (FCs) composed of dendritic and genetically engineered NIH3T3 cells were prepared with polyethylene glycol, and fusion efficiency was 30.3%. Prior immunization with FCs prevented tumor formation upon challenge with B16 tumor cells. Efficacy was reduced when studies were performed in mice depleted of NK cells. Vaccination with FCs containing DCs and fibroblasts transfected with denatured DNA did not inhibit tumor growth. Cytotoxic T cell (CTL) activity of spleen cells from immunized mice against both Yac-1 and tumor cells was also stimulated by administration of FCs compared with the activity observed for cells obtained from naïve mice. These data demonstrate the therapeutic efficacy of fusion cell-based vaccine therapy using syngeneic DCs and allogeneic fibroblasts transfected with tumor-derived genomic DNA.
基于先前的多项研究表明基因组DNA转染可稳定改变摄取外源DNA的细胞特性，我们研究了用B16肿瘤细胞基因组DNA转染的同基因树突状细胞（DC）与异基因成纤维细胞（NIH3T3）融合所赋予的抗肿瘤免疫力。用聚乙二醇制备由树突状细胞和基因工程化的NIH3T3细胞组成的融合细胞（FC），融合效率为30.3%。用FC预先免疫可在受到B16肿瘤细胞攻击时预防肿瘤形成。当在NK细胞耗竭的小鼠中进行研究时，疗效降低。用含有经变性DNA转染的DC和成纤维细胞的FC进行疫苗接种不能抑制肿瘤生长。与从未免疫小鼠获得的细胞的活性相比，给予FC也刺激了免疫小鼠脾细胞对Yac-1和肿瘤细胞的细胞毒性T细胞（CTL）活性。这些数据证明了使用经肿瘤衍生基因组DNA转染的同基因DC和异基因成纤维细胞的基于融合细胞的疫苗疗法的治疗效果。
