| Project/Area Number |
18591440
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 |
MORISAKI Takashi Kyushu University, Faculty of Medical Sciences, Contracted Research Associate (90291517)
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| Co-Investigator(Kenkyū-buntansha) |
KATANO Mitsuo Kyushu University, Faculty of Medical Sciences, Professor (10145203)
BABA Eishi Kyushu University, University Hospital, Assistant Professor (00315475)
KOJIMA Masasyuki Kyushu University, University Hospital, Assistant Professor (90380394)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,730,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Dendritic cells / Exosomes / Vaccine / Standard / Cancer therapy / Molecule transplantation |
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| Research Abstract |
Aim of this study is to develop a method for preparing dendritic cells (DCs), which have homogeneous ability of antigen presentation between individuals, as therapeutic tool for cancer patients. It is a unique point that exosomes secreted by DCs generated from healthy volunteers' peripheral blood mononuclear cells (PBMCs) are utilized for this ourpose.
Data obtained during the research period are as follows:
1) Methodology for qualitative and quantitative evaluation of DC-derived exosomes:
We developed a new methodology for purification and qualitative and quantitative evaluation of exosomes by combination of ultracentrifugation, sucrose density, and BDLA-DR-bound beads. As a result, it was shown tat critical antigen presentation-related molecules, including MHC class II, CD80, CD86, and ICAM-1, are expressed highly and homogeneously on exosomes derived from healthy volunteer's DCs. On the other hand, expressions of these molecules were weak on exosomes derived from patient-derived DCs.In conclusion, it was strongly indicated that expression of HLA-DR on purified exosomes is a marker for qualitative and quantitative evaluation of DC-derived exosomes.
2)Effects of DC"derived exosomes on differentiation and function of DCs:
2-1: Survival prolongation of CD4+ T cells by exosomes collected from healty volunteer-derived DCs.
2-2: Improved differentiation of patient-derived DCs by exosomes collected from healty volunteerderived DCs.
2-3 increased NK cell activity by exosomes collected from healty volunteerderived DCs.
2-4: Induction of cytotoxic T cells (CTLs) by exosomes collected from tumor cell-pulsed DCs.
2-5: Survival prolongation of regulatory T cells by exosomes collectede from malignant effusions.
3)Others:
An interesting possibility that exosomes secreted from CE4-transfected DCs express CEA was indicated.
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