Department of Urological Surgery, The Second Affiliated Hospital, Chongqing Medical University, Yuzhong District, Chongqing, PRC 400010, China.
Cell Immunol. 2010;262(2):112-9. doi: 10.1016/j.cellimm.2010.01.004. Epub 2010 Feb 1.
Dendritic cells (DC), as professional antigen presenting cells, play the central role in the process of body initiating the anti-tumor immunity, and the study on DC anti-tumor vaccine has become heated in recent years. In this study, we used polyethylene glycol (PEG) to induce renal cell carcinoma (RCC) 786-O cell line fused with peripheral blood DC of healthy volunteers, and discuss the biological characteristics of fusion vaccine and its anti-tumor effects in vitro and in human immune reconstituted SCID mice model of RCC. The study found that PEG could effectively induce cell fusion, and the expressions of CD86 and HLA-DR in fusion vaccine group were significantly up-regulated compared with the DC control group; the secretion of IL-12 was much higher and longer than that of the control; the functions of dendritic cell-tumor fusion vaccine to stimulate the proliferation of allogenic T lymphocytes and to kill RCC786-O cells in vitro were significantly higher than those of the control group, and after the killing, apoptosis body was observed in the target cells; after the injection of fusion vaccine into human immune reconstituted SCID mice model of RCC786-O via vena caudalis, the volume of mice tumor was reduced significantly, proliferation index of tumor cells decreased obviously compared with that of the control group, and more hemorrhage and putrescence focuses presented, accompanying large quantity of lymphocytes soakage. The results of this experimental study shows that fusion vaccine of RCC786-O cell line and DC can significantly stimulate the proliferation of allogenic T cells and specifically inhibit and kill RCC cells in vitro and in vivo, which makes the DC-RCC786-O fusion vaccine a possible new way of effective RCC immunotherapy.
树突状细胞(DC)作为专业的抗原提呈细胞,在机体启动抗肿瘤免疫过程中发挥着核心作用,近年来,DC 抗肿瘤疫苗的研究成为热点。本研究采用聚乙二醇(PEG)诱导肾癌细胞(RCC)786-O 细胞与人外周血 DC 融合,探讨融合疫苗的生物学特性及其在体外和人源免疫重建 SCID 小鼠 RCC 模型中的抗肿瘤作用。研究发现,PEG 可有效诱导细胞融合,融合疫苗组 CD86 和 HLA-DR 的表达明显高于 DC 对照组;IL-12 的分泌量更高、持续时间更长;树突状细胞-肿瘤融合疫苗刺激同种异体 T 淋巴细胞增殖和杀伤 RCC786-O 细胞的功能明显高于对照组,杀伤后可见靶细胞凋亡小体;融合疫苗尾静脉注入人源免疫重建 SCID 小鼠 RCC786-O 模型后,明显缩小小鼠肿瘤体积,与对照组相比,肿瘤细胞增殖指数明显降低,且出现更多出血和坏死灶,伴有大量淋巴细胞浸润。该实验研究结果表明,RCC786-O 细胞系与 DC 的融合疫苗可明显刺激同种异体 T 细胞增殖,并在体外和体内特异性抑制和杀伤 RCC 细胞,使 DC-RCC786-O 融合疫苗成为一种有效的 RCC 免疫治疗的新途径。