Kitadani Junya, Ojima Toshiyasu, Iwamoto Hiromitsu, Tabata Hiroaki, Nakamori Mikihito, Nakamura Masaki, Katsuda Masahiro, Miyazawa Motoki, Hayata Keiji, Yamaue Hiroki
Second Dept. of Surgery, Wakayama Medical University, School of Medicine.
Gan To Kagaku Ryoho. 2016 Sep;43(9):1071-3.
The difficulty in obtaining a sufficient number of functional dendritic cells(DCs)is a well-known serious problem in DCbased immunotherapy. Therefore, we used induced pluripotent stem cell-derived DCs(iPSDCs). We have reported that mouse iPSDCs are equivalent to BMDCs, in terms of maturation and antigen presentation. In this study, the antitumor immune response of human iPSDCs expressing the carcinoembryonic antigen was examined, to determine its clinical application in gastrointestinal cancer. Human iPS cells were established from healthy human fibroblasts using a Sendai virus vector, and human iPSDCs were differentiated under a feeder-free culture. Additionally, the surface marker expression, cytokine production, and migratory capacity of human iPSDCs were equivalent to those of monocyte-derived DCs(MoDCs). After 3 cycles of stimulation of autologous PBMCs by genetically modified DCs, the 51Cr-release assay was performed. The lymphocytes stimulated by iPSDCs-CEA showed cytotoxic activity against LCL-CEA and CEA652-pulsed LCL, but showed no cytotoxicity against LCL-LacZ. In addition, they showed cytotoxic activity against CEA-positive human cancer cell lines, MKN45 and HT29, but showed no cytotoxicity against CEA-negative human cancer cell line MKN1. In conclusion, CEA-specific CTLs responses could be induced by iPSDCs-CEA. This vaccination strategy may be useful in future clinical applications of cancer vaccines.
在基于树突状细胞（DC）的免疫治疗中，难以获得足够数量的功能性树突状细胞是一个众所周知的严重问题。因此，我们使用了诱导多能干细胞衍生的树突状细胞（iPSDCs）。我们已经报道，小鼠iPSDCs在成熟和抗原呈递方面与骨髓来源的树突状细胞（BMDCs）相当。在本研究中，检测了表达癌胚抗原的人iPSDCs的抗肿瘤免疫反应，以确定其在胃肠道癌中的临床应用。使用仙台病毒载体从健康人成纤维细胞中建立人iPS细胞，并在无饲养层培养条件下分化出人iPSDCs。此外，人iPSDCs的表面标志物表达、细胞因子产生和迁移能力与单核细胞衍生的树突状细胞（MoDCs）相当。在通过基因改造的DC对自体PBMC进行3个周期的刺激后，进行了51Cr释放试验。由iPSDCs-CEA刺激的淋巴细胞对LCL-CEA和CEA652脉冲的LCL显示出细胞毒性活性，但对LCL-LacZ没有细胞毒性。此外，它们对CEA阳性的人癌细胞系MKN45和HT29显示出细胞毒性活性，但对CEA阴性的人癌细胞系MKN1没有细胞毒性。总之，iPSDCs-CEA可以诱导CEA特异性CTL反应。这种疫苗接种策略可能在未来癌症疫苗的临床应用中有用。
