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Application and analysis the effect of chemoimmunotherapy by doxorubicin in mouse neuroblastoma model

Research Project

Project/Area Number 15K10927
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatric surgery
Research InstitutionSaitama Medical University

Principal Investigator

Seiichiro Inoue  埼玉医科大学, 医学部, 准教授 (70431690)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords神経芽腫 / 小児外科 / 腫瘍免疫 / Chemoimmunotherapy / 神経芽細胞腫 / 腫瘍免疫学 / 免疫療法 / chemoimmunotherapy / 細胞治療
Outline of Final Research Achievements

Combination immunotherapy with conventional intensive therapy for advanced neuroblastoma is the hopeful new therapy. To establish new intensive multimodal therapeutic regimen, we applied the concept of chemoimmunotherapy. Firstly, we demonstrated that doxorubicin induces immunogenic cell death in vitro. Using died neuroblastoma cell which induced immunogenicity, we successfully generate antigen presenting cell (APC) which can induce antitumor immune reaction, by co-culturing died neuroblastoma cell treated and doxorubicin and bone marrow cell with GM-CSF, IL-4 and CpG-ODN. This APC can promote IFN-g production by CD8a+ lymphocytes in co-culture with doxorubicin treated neuroblastoma cell, and can suppress the progression of intravenously injected neuroblastoma by the induction of antitumor immune reaction in vivo. We analyzed the cell surface antigen expression on this APC and showed that the pattern of cell surface antigen expression is compatible with activated dendritic cells.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (6 results)

All 2017 2016 2015

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] hemoimmunotherapeutic effect of combined treatment with ex vivo generated antigen-presenting immune cells and conventional antitumor agents in a mouse neuroblastoma model2017

    • Author(s)
      Inoue S, Setoyama Y, Odaka A, Kitagawa D, Bech Y
    • Journal Title

      J Pediar Surg

      Volume: 52 Issue: 10 Pages: 1642-1650

    • DOI

      10.1016/j.jpedsurg.2017.04.006

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ex vivo induction of antitumor DEC-205+ CD11c+ cells in a murine neuroblastoma model by co-stimulation with doxorubicin, lipopolysaccharide and interleukin-42016

    • Author(s)
      Inoue S, Setoyama Y, Bech Y, Kitagawa D, Odaka A,
    • Journal Title

      Biomed Rep

      Volume: 4 Pages: 27-32

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Flt-3 ligandによる抗腫瘍免疫細胞誘導とマウス神経芽腫細胞に対する免疫応答の基礎研究2017

    • Author(s)
      160.井上成一朗、瀬戸山由美子、小高明雄、北川大輝、別宮好文
    • Organizer
      第54回日本小児外科学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Generation of anti-tumor CD11c+ cells from bone marrow by applying the chemoimmunotherapeutic concept in mouse neuroblastoma model2016

    • Author(s)
      Inoue S, Odaka A, Setoyama Y, Kitagawa D, Beck Y:
    • Organizer
      The 24th congress of the Asian Association of Pediatric Surgeons
    • Place of Presentation
      ヒルトン福岡シーホーク
    • Year and Date
      2016-05-24
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Immunogenic cell death誘導神経芽腫細胞を介した抗腫瘍反応誘導を司る自然免疫細胞の解析とTLR刺激の効果の検討2016

    • Author(s)
      井上成一朗、小高明雄、瀬戸山由美子、北川大輝、別宮好文
    • Organizer
      第116回 日本外科学会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2016-04-14
    • Related Report
      2016 Research-status Report
  • [Presentation] TLR-4刺激とIL-4によるDEC205陽性樹状細動誘導と神経芽腫に対する抗腫瘍効果2015

    • Author(s)
      井上成一朗、小高明雄、瀬戸山由美子、別宮好文
    • Organizer
      第52回日本小児外科学会学術集会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-05-28
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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