2007 Fiscal Year Final Research Report Summary
Development of DC-based vaccine therapy by utilizing exosomes collected from healthy volunteer-derived DCs
| 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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| 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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[Journal Article] Regulatory T cells are possible effect prediction markers of immunotherapy for cancer patients
Author(s)
Wada, J, Yamasaki, A, Morisaki, T, Nagai, S, Yanai, K, Fuchino, K, Akiyoshi, T, Koga, K, Nakashima, H, Nakamura, M, Tanaka, M, Katano, M
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Journal Title
Anticancer Research (in press)
Description
「研究成果報告書概要(欧文)」より
