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Cancer Immunotherapy Targeting B7-DC/ B7-H1/ PD-1 interaction May Improve Tumor Microenviroment

Research Project

Project/Area Number 21591641
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

YOSHIMURA Kiyoshi  山口大学, 医学部附属病院, 助教 (30346564)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords腫瘍免疫 / 補助シグナル / 抗体療法 / 癌 / 免疫療法
Research Abstract

B7-H1 is a co-signal to modulate immune check point expressed on both subsets of immune effector cells and cancer. B7-H1 is able to induce an anergy of CD8+ T cells through the PD-1 receptor leading to tumor growth and immune suppression. Blockade of B7-H1 with neutralizing antibody is a novel therapy which alters tumor microenvironment. The antibody blockade of this B7-H1/ PD-1 interaction may result in the alteration of immune response and tumor microenvironment preventing tumor evasion from the immune system. Materials and Methods:
BALB/ C mice were challenged with colorectal hepatic metastases and then treated with an attenuated Listeria monocytogenes(LM) vaccine platform in combination with B7-H1 blocking antibody. Mice were investigated for survival, immunological analysis with flow cytometry and in vitro assay
Results : Mice treated with B7-H1+ LM had 70% survival. The analysis of immune subsets demonstrated an increase in expression of B7-H1 on CD8+ T cells of mice treated with LM. In vitro analysis of CD8+ T cell activation showed an increase of 50% in the presence of tumor with B7-H1 blocking antibody.
Discussion : B7-H1 blockade showed increased survival by preventing the inhibitory signaling between T cells, dendritic cells and tumor.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (10 results)

All 2011 2010 2009

All Journal Article (2 results) Presentation (8 results)

  • [Journal Article] 消化器外科セミナー世界における癌免疫療法のトピックスと課題2011

    • Author(s)
      吉村清、岡正朗
    • Journal Title

      消化器外科

      Volume: 34巻1号 Pages: 107-112

    • Related Report
      2011 Final Research Report
  • [Journal Article] 消化器外科セミナー世界における癌免疫療法のトピックスと課題2011

    • Author(s)
      吉村清, 岡正朗
    • Journal Title

      消化器外科

      Volume: 34巻 Pages: 107-112

    • Related Report
      2011 Annual Research Report
  • [Presentation] B7-H1/ PD-1 interactionをターゲットとした癌免疫療法(Cancer Immunotherapy Targeting B7-H1/ PD-1 interaction Improves Tumor Microenviroment)2011

    • Author(s)
      吉村清、新藤芳太郎、渡邊裕策、前田祥成、前田訓子、井上萌子、山本滋、吉野茂文、硲彰一、岡正朗
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋国際会議場(愛知)
    • Year and Date
      2011-10-03
    • Related Report
      2011 Final Research Report
  • [Presentation] B7-H1/PD-1 interactionをターゲットとした癌免疫療法2011

    • Author(s)
      吉村清
    • Organizer
      第70回日本癌学会
    • Place of Presentation
      名古屋国際会議場(愛知)
    • Year and Date
      2011-10-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] Immune check point inhibitionを用いた免疫療法2011

    • Author(s)
      吉村清、新藤芳太郎、渡邊裕策、前田祥成、前田訓子、山本滋、吉野茂文、硲彰一、岡正朗
    • Organizer
      第66回日本消化器外科学会総会
    • Place of Presentation
      名古屋国際会議場(愛知)
    • Year and Date
      2011-07-14
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 明日の外科医療を構築するための基礎研究B7-H1/ PD-1 interactionをターゲットとしImmune check point inhibitionを目的とした免疫療法2011

    • Author(s)
      吉村清、新藤芳太郎、渡邊祐策、前田祥成、亀井滝士、前田訓子、鈴木伸明、山本滋、吉野茂文、硲彰一、岡正朗
    • Organizer
      第111回日本外科学会総会
    • Place of Presentation
      震災の為紙上発表
    • Year and Date
      2011-05-25
    • Related Report
      2011 Final Research Report
  • [Presentation] 明日の外科医療を構築するための基礎研究B7-H1/PD-1 interactionをターゲットとしImmune check point inhibitionを目的とした免疫療法2011

    • Author(s)
      吉村清
    • Organizer
      第111回日本外科学会総会
    • Place of Presentation
      (震災のため誌上発表)
    • Year and Date
      2011-05-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] B7-H1/ PD-1をターゲットとした消化器癌肝転移に対する免疫療法2010

    • Author(s)
      吉村清、硲彰一、岡正朗
    • Organizer
      第14回日本がん免疫学会総会
    • Place of Presentation
      KKRホテル熊本(熊本)
    • Year and Date
      2010-07-22
    • Related Report
      2011 Final Research Report
  • [Presentation] Modulation of immune checkpoint B7-H1/B7-DC/PD-1 interaction in combination with live attenuated Listeria monocytogenes effectively treats hepatic colorectal cancer metastases2010

    • Author(s)
      吉村清
    • Organizer
      アメリカ癌学会
    • Place of Presentation
      米国、ワシントンDCコンベンションセンター
    • Year and Date
      2010-04-19
    • Related Report
      2009 Annual Research Report
  • [Presentation] エフェクターメカニズムに立脚したバイオセラピィエフェクターメカニズムに基づき、副刺激・調節系因子をターゲットとした消化器癌肝転移に対する免疫療法2009

    • Author(s)
      吉村清、硲彰一、岡正朗
    • Organizer
      第22回日本バイオセラピィ学会
    • Place of Presentation
      スイスホテル南海大阪(大阪)
    • Year and Date
      2009-11-26
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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