Development of the new cancer immunotherapy using fusion cell-vaccine of iPSDC and cancer stem cell

使用iPSDC和癌症干细胞的融合细胞疫苗开发新的癌症免疫疗法

• 批准号: 23591874
• 负责人: NAKAMURA Masaki
• 金额: $ 3.33万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591874/
• 关键词: ｉＰＳ細胞; 樹状細胞; 癌免疫療法; iPS細胞; 癌幹細胞

It is generally accepted that the difficulty in obtaining a sufficient number of functional dendritic cells (DCs) is a serious problem in DC-based immunotherapy. We used the induced pluripotent stem (iPS) cell-derived DCs (iPSDCs). In this study, we examined the capacity of iPSDCs compared with that of bone marrow-derived DCs (BMDCs). We adenovirally transduced the hgp100 gene into DCs and immunized mice once with the genetically modified DCs. The cytotoxic activity of CD8 (+) cytotoxic T lymphocytes (CTLs) and the therapeutic efficacy of the vaccination were assayed. Our results showed that hgp100-specific CTLs exhibited as high a level of cytotoxicity as BMDCs. Moreover, vaccination with the genetically modified iPSDCs achieved as high a level of therapeutic efficacy as vaccination with BMDCs. This study clarified experimentally that iPSDCs have an equal capacity to BMDCs. This vaccination strategy may therefore be useful for future clinical application as a cancer vaccine.

人们普遍认为，难以获得足够数量的功能性树突状细胞（DC）是基于DC的免疫治疗中的一个严重问题。我们使用了诱导多能干（iPS）细胞衍生的DC（iPSDCs）。在这项研究中，我们检查了iPSDCs的能力与骨髓来源的DC（BMDCs）相比。我们用腺病毒将hgp100基因转导入DCs中，并用基因修饰的DCs免疫小鼠一次。检测CD8（+）细胞毒性T淋巴细胞（CTL）的细胞毒活性和疫苗的治疗效果。我们的研究结果表明，hgp100特异性CTL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。该研究通过实验阐明了iPSDCs具有与BMDC相同的容量。因此，这种疫苗接种策略可能有助于未来作为癌症疫苗的临床应用。