RRC ID 44508
著者 Iwamoto H, Ojima T, Hayata K, Katsuda M, Miyazawa M, Iida T, Nakamura M, Nakamori M, Iwahashi M, Yamaue H.
タイトル Antitumor immune response of dendritic cells (DCs) expressing tumor-associated antigens derived from induced pluripotent stem cells: in comparison to bone marrow-derived DCs.
ジャーナル Int J Cancer
Abstract 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 (51) Cr-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.
巻・号 134(2)
ページ 332-41
公開日 2014-1-15
DOI 10.1002/ijc.28367
PMID 23824921
MeSH Adenoviridae / genetics Animals Bone Marrow / immunology* Bone Marrow / pathology Cells, Cultured Cytokines / metabolism Dendritic Cells / immunology* Dendritic Cells / pathology Embryo, Mammalian / cytology Embryo, Mammalian / immunology Female Fibroblasts / cytology Fibroblasts / immunology Flow Cytometry Humans Induced Pluripotent Stem Cells / immunology* Induced Pluripotent Stem Cells / pathology Melanoma, Experimental / immunology* Melanoma, Experimental / pathology Melanoma, Experimental / prevention & control Mice Mice, Inbred C57BL T-Lymphocytes, Cytotoxic / immunology T-Lymphocytes, Cytotoxic / pathology gp100 Melanoma Antigen / genetics gp100 Melanoma Antigen / immunology*
IF 5.145
引用数 14
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 YAC-1