Cancer vaccine therapy using genetically modified induced pluripotent stem cell-derived dendritic cells expressing the TAA gene.

我们从iPS细胞开发了诱导的多能干细胞衍生的树突状细胞DC（iPSDC），并且除了iPSDC迁移到淋巴结的能力之外，还检查了iPSDC与骨髓衍生的DC（BMDC）相比的成熟能力。我们用腺病毒将天然肿瘤抗原hgp100基因转导入DCs中，并用基因修饰的DCs免疫小鼠一次。我们的研究结果表明，iPSDCs在成熟和迁移方面与BMDCs具有相同的能力。此外，在用遗传修饰的iPSDCs免疫的小鼠中产生hgpl00特异性CTL。这些CTL对B16细胞表现出与BMDC一样高的细胞毒性水平。此外，用遗传修饰的iPSDC接种实现了与用BMDC接种一样高的治疗功效水平。我们的研究阐明了基因修饰的iPSDCs在肿瘤相关抗原特异性治疗性抗肿瘤免疫方面具有与BMDC相同的能力。

We developed the induced pluripotent stem cell-derived dendritic cells DCs (iPSDCs) from iPS cells and examined the capacity for maturation of iPSDCs compared to that of bone marrow-derived DCs (BMDCs) in addition to the capacity for migration of iPSDCs to lymph nodes. We adenovirally transduced the hgp100 gene, natural tumor antigens, into DCs and immunized mice once with the genetically modified DCs. Our results showed that iPSDCs have an equal capacity to BMDCs in terms of maturation and migration. Furthermore, hgp100-specific CTLs were generated in mice immunized with genetically modified iPSDCs. These CTLs exhibited as high a level of cytotoxicity against B16 cells as BMDCs. Moreover, vaccination with the genetically modified iPSDCs achieved as high a level of therapeutic efficacy as vaccination with BMDCs. Our study clarified that genetically modified iPSDCs have an equal capacity to BMDCs in terms of tumor-associated antigen specific therapeutic antitumor immunity.