| Project/Area Number |
23650609
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor immunology
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
AWAI Hirotake 熊本大学, 大学院・生命科学研究部, 助教 (10433020)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | iPS 細胞 / 樹状細胞 / がん抗原 / 腫瘍免疫 / がん免疫療法 / T 細胞 / iPS細胞 / Ｔ細胞 / 拒絶反応回避 |
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| Research Abstract |
We established a method by which we can obtain a large number of functional dendritic cells (DC)with a simple procedure from human iPS cells. We transduced iPS cell-derived CD11b+myeloid cellswith cMYC and BMI1 genes associated with proliferative or anti-senescence effects. This made the cellscapable of propagating for more than 4 months in an M-CSF-dependent manner while retaining thecapacity to differentiate into DC. We named the iPS cell-derived proliferating myeloid cells “iPS-ML”,and the iPS-ML-derived dendritic cells “ML-DC”. In addition, we generated T AP2-deficient iPS cellclones by zinc finger nuclease-aided targeted gene disruption. T AP2-deficient iPS-ML avoidedrecognition by pre-activated allo-reactive CD8+T cells. The T AP2-deficient ML-DC expressingexogenously introduced HLA-A2 genes stimulated HLA-A2-restricted tumor antigen-specific CD8+Tcells obtained from HLA-A2-positive allogeneic donors, resulting in generation of tumorantigen-specific CTL lines. T AP-deficient iPS-ML introduced with various HLA class I genes may serveas an unlimited source of DC for vaccination therapy . Based on the present study , we propose aDC-producing system, which is simple, safe, and applicable to any patients irrespective of their HLAtypes. This technology will pave the way for the mass production of DC for therapeutic use. We havealso succeeded in inhibition of tumor growth of intraperitoneal dissemination of human cancer cells inimmune-deficient mice by intraperitoneal injection of human iPS-macrophage genetically modified tosecrete interferon-beta.
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