論文 - 詳細
| RRC ID | 50647 |
|---|---|
| 著者 | Kitadani J, Ojima T, Iwamoto H, Tabata H, Nakamori M, Nakamura M, Hayata K, Katsuda M, Miyajima M, Yamaue H. |
| タイトル | Cancer Vaccine Therapy Using Carcinoembryonic Antigen - expressing Dendritic Cells generated from Induced Pluripotent Stem Cells. |
| ジャーナル | Sci Rep |
| Abstract |
Clinical application of dendritic cell (DC) vaccine therapy is hindered by the need for a large quantity of DCs generated from peripheral blood monocytes of the patient. We investigated whether genetically modified human induced pluripotent stem cell (iPSC)-derived dendritic cells (hiPSDCs) expressing carcinoembryonic antigen (CEA) could induce CEA-specific cytotoxic T cells in a human model and whether genetically modified mouse iPSDCs (miPSDCs) expressing CEA showed an actual antitumor effect using a CEA transgenic mouse model. We differentiated hiPSDCs from iPSCs of three healthy donors and transduced CEA cDNA into the hiPSDCs. The surface marker expression, cytokine secretion and migratory capacity of the hiPSDCs were equivalent to those of human monocyte-derived DCs (hMoDCs). Cytotoxic T cells activated by hiPSDCs-CEA exhibited CEA-specific cytotoxic activity against the target cells expressing CEA. Furthermore, in the CEA transgenic mouse model, cytotoxic T cells activated in mice immunized with miPSDCs-CEA displayed CEA-specific cytotoxic activity against MC38-CEA. In the subcutaneous tumour model, vaccination with miPSDCs-CEA achieved a significant growth inhibitory effect on MC38-CEA. No adverse events caused by the administration of miPSDCs were observed. Genetic modification of iPSDCs, inducing the expression of CEA, is a promising tool for clinical applications of vaccine therapy for treating gastrointestinal cancer patients. |
| 巻・号 | 8(1) |
| ページ | 4569 |
| 公開日 | 2018-3-15 |
| DOI | 10.1038/s41598-018-23120-z |
| PII | 10.1038/s41598-018-23120-z |
| PMID | 29545628 |
| PMC | PMC5854614 |
| MeSH | Animals Cancer Vaccines / immunology* Carcinoembryonic Antigen / genetics Carcinoembryonic Antigen / immunology Carcinoembryonic Antigen / metabolism* Cells, Cultured Dendritic Cells / cytology Dendritic Cells / metabolism* Dendritic Cells / transplantation Humans Induced Pluripotent Stem Cells / cytology* Interferon-gamma / metabolism Interleukin-12 / metabolism Mice Mice, Inbred C57BL Mice, Transgenic Skin Neoplasms / immunology Skin Neoplasms / pathology Skin Neoplasms / prevention & control* Spleen / cytology T-Lymphocytes, Cytotoxic / immunology |
| IF | 3.998 |
| 引用数 | 7 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 12 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | iPS-MEF-Ng-20D-17(APS0001) |