Antitumor immune response of dendritic cells (DCs) expressing tumor-associated antigens derived from induced pluripotent stem cells: In comparison to bone marrow-derived DCs
Antitumor immune response of dendritic cells (DCs) expressing tumor-associated antigens derived from induced pluripotent stem cells: In comparison to bone marrow-derived DCs
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DOI：
10.1002/ijc.28367
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发表时间：
2014-01-15
影响因子：
6.4
通讯作者：
Yamaue, Hiroki
中科院分区：
文献类型：
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作者：
Iwamoto, Hiromitsu;Ojima, Toshiyasu;Yamaue, Hiroki
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。因此，我们使用诱导多能干（iPS）细胞衍生的DC（iPSDCs）。如果iPSDCs的治疗效果与骨髓来源的DC（BMDC）的治疗效果相当，则可以解决上述问题。在我们的研究中，我们从iPS细胞诱导iPSDCs，并检查了iPSDCs与BMDC相比的成熟能力以及iPSDCs迁移到局部淋巴结的能力。我们用腺病毒将天然肿瘤抗原hgp 100基因转导入DCs中，并用基因修饰的DCs免疫小鼠一次。使用Cr-51释放试验测定CD 8（+）细胞毒性T淋巴细胞（CTL）的细胞毒性活性。在皮下肿瘤模型中检查疫苗接种的治疗功效。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hgpl 00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。我们的研究通过实验阐明，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。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。
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. Therefore, we used the induced pluripotent stem (iPS) cell-derived DCs (iPSDCs). If the therapeutic efficacy of iPSDCs is equivalent to that of bone marrow-derived DCs (BMDCs), then the aforementioned problems may be solved. In our study, we induced iPSDCs from iPS cells and examined the capacity for maturation of iPSDCs compared to that of BMDCs in addition to the capacity for migration of iPSDCs to regional lymph nodes. We adenovirally transduced the hgp100 gene, natural tumor antigens, into DCs and immunized mice once with the genetically modified DCs. The cytotoxic activity of CD8 (+) cytotoxic T lymphocytes (CTLs) was assayed using a Cr-51-release assay. The therapeutic efficacy of the vaccination was examined in a subcutaneous tumor model. 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 experimentally that genetically modified iPSDCs have an equal capacity to BMDCs in terms of tumor-associated antigen-specific therapeutic antitumor immunity. This vaccination strategy may therefore be useful for future clinical application as a cancer vaccine.