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Development of DC-based vaccine therapy by utilizing exosomes collected from healthy volunteer-derived DCs

Research Project

Project/Area Number 18591440
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKyushu University

Principal Investigator

MORISAKI Takashi  Kyushu University, Faculty of Medical Sciences, Contracted Research Associate (90291517)

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)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
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)
KeywordsDendritic cells / Exosomes / Vaccine / Standard / Cancer therapy / Molecule transplantation
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.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (5 results)

All 2007 2006 Other

All Journal Article (3 results) Presentation (2 results)

  • [Journal Article] Activated Src and Ras induce gefitinib resistance by activation of signaling pathways downstream of epidermal growth factor receptor in human gallbladder adenocarcinoma cells.2006

    • Author(s)
      Qin B et al.
    • Journal Title

      Cancer Chemother Pharmacol 58

      Pages: 577-584

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Regulatory T cells are possible effect prediction markers of immunother apy for cancer patients

    • Author(s)
      Wada J, et. al.
    • Journal Title

      Anticancer Research (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Journal Title

      Anticancer Research (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 担癌間者胸腹水中の制御性T細胞(Treg細胞)増加の機序解析2007

    • Author(s)
      和田 純治, ほか
    • Organizer
      第20回 日本バイオセラピィ学会総会
    • Place of Presentation
      札幌プリンスホテル
    • Year and Date
      2007-10-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] 癌患者末梢血中の制御性T細胞(Treg細胞)増加の機序解析と癌免疫療法におけるTreg細胞測定の臨床的意義2007

    • Author(s)
      和田 純治, ほか
    • Organizer
      第107 回日本外科学会総会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2007-04-12
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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