| Project/Area Number |
17390351
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KATANO Mitsuo Kyushu University, Faculty of Medical Sciences, Professor, 大学院医学研究院, 教授 (10145203)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Masafumi Kyushu University, Faculty of Medical Sciences, Associate Professor, 大学院医学研究院, 助教授 (30372741)
MORISAKI Takashi Kyushu University, Faculty of Medical Sciences, Contracted Research Associate, 大学院医学研究院, 非常勤講師 (90291517)
NOMURA Masatoshi Kyushu University, University Hospital, Research Associate, 病院・助手 (30315080)
TANI Kenzaburou Kyushu University, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (00183864)
SUEISHI Katsuo Kyushu University, Faculty of Medical Sciences, Professor, 大学院医学研究院, 教授 (70108710)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2006: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2005: ¥10,200,000 (Direct Cost: ¥10,200,000)
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| Keywords | Exosomes / Small vesicles / Dendritic cells / Vaccine therapy / Immunotherapy / Cancerous ascites / Regulatory T cells / Functional molecules / 細胞小胞 / 免役療法 / 悪性腫瘍 / 癌性腹膜炎 |
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| Research Abstract |
Along a study plan, we report here results of research during the study period. 1. Making of high exosome-secretion cells : Monocyte-derived dendritic cells (DCs) secrete a large amount of exosomes and their secretion is stable. 2. Separation and purification of Exosomes : DCs-derived exosomes and tumor-derived exosomes were efficiently purified by anti-HLA DR antibodies and by the antibodies against tumor antigens, respectively. 3. Change to functional vesicles of exosomes : We introduced EGFR or CEA gene using adenovirus vectors to DCs. These DCs secreted exosomes expressing EGFR or CEA, respectively. In other words, the possibility that could produce arbitrary protein on exosome by gene transfection was shown. 4. Molecular biologic analysis of exosomes : It was confirmed that tumor-derived exosomes secrete various kinds of protein which are useful for cancer vaccine. Thus, a utility of tumor-derived exosomes as nanoparticle for supplying carcinoma-related molecules was confirmed. 5. Immunological functional analysis of exosomes : DCs-derived exosomes : 1) augmentation of natural killer cells activity, 2) functional improvement of cancer patients-derived DCs, and 3) survival prolongation of regulatory T cells. Cancer cell-derived exosomes : Induction of CTL-like cells. As described above, we clarified several unique biological and immunological characteristics of exosomes and suggested a clinical application of exosomes to tumor immunotherapy. On the other hand, it was a plan to express Patched on exosomes at first, but did not succeed. However, during this study period, we succeeded in making several anti-Patched antibodies that have neutralization activity.
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