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Establishment of cancer antigen-specific CTL therapy by a concomitant functional regulation of CTL and regulatory T cell and an inhibition of T cell differentiation

Research Project

Project/Area Number 24591973
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionShiga University of Medical Science

Principal Investigator

MURATA Satoshi  滋賀医科大学, 医学部, 講師 (90239525)

Co-Investigator(Kenkyū-buntansha) TANI Tohru  滋賀医科大学, 医学部, その他(特任教授) (20179823)
KURUMI Yoshimasa  滋賀医科大学, 医学部, 教授 (70205219)
SHIMIZU Tomoharu  滋賀医科大学, 医学部, 助教 (70402708)
MIYAKE Tohru  滋賀医科大学, 医学部, その他(客員助教) (70581924)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords腫瘍免疫 / 免疫治療 / 癌ワクチン / T細胞補助刺激 / 細胞治療 / 養子免疫 / CTL / OX40 / B7DC / がん免疫治療 / がんワクチン / エフェクター細胞 / 補助刺激 / 癌免疫治療
Outline of Final Research Achievements

We have done the research to develop the efficient cancer-specific CTL therapy, which was to generate CTLs ex vivo and to transfer them into patients.
Cancer-specific CTLs were efficiently generated when T cells were cultured with a cancer antigen and OX40 costimulation that could enhance the effector T cell function. When these cancer-specific CTLs were adoptively transferred into the tumor-bearing mice pretreated with OX40 costimulation that could also inhibit the regulatory T cell function, CTLs could overcome immune tolerance condition, maintain its function, and finally eliminate tumor. IL-2 and/or B7-DC proved to be important molecules that could contribute to the generation of effective CTLs.
Human lymphocytes from the volunteers could generate antigen (HA)-specific CTLs when cultured with an antigen and OX40 stimulation. From these findings, we believe that cancer-specific CTL therapy treated with costimulatory molecules can be applied in a clinical setting in future.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (7 results)

All 2014 2013

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (5 results)

  • [Journal Article] Surgery-Induced Peritoneal Cancer Cells in Patients Who Have Undergone Curative Gastrectomy for Gastric Cancer.2014

    • Author(s)
      Takebayashi K, Murata S, Yamamoto H, Ishida M, Yamaguchi T, Kojima M, Shimizu T, Shiomi H, Sonoda H, Naka S, Mekata E, Okabe H, Tani T.
    • Journal Title

      Ann Surg Oncol

      Volume: 21 Issue: 6 Pages: 1991-1997

    • DOI

      10.1245/s10434-014-3525-9

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fusion protein of mutant B7-DC and Fc enhances the antitumor immune effect of GM-CSF-secreting whole-cell vaccine.2014

    • Author(s)
      Kojima M, Murata S, Mekata E, Takebayashi K, Jaffee EM, Tani T.
    • Journal Title

      J Immunother

      Volume: 37(3) Issue: 3 Pages: 147-154

    • DOI

      10.1097/cji.0000000000000025

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Curative surgery for gastric cancer induces peritoneal metastasis2014

    • Author(s)
      Satoshi Murata, Katsushi Takebayashi, Hiroshi Yamamoto, Mitsuaki Ishida, Tsuyoshi Yamaguchi, Sachiko Kaida, Tomoharu Shimizu, Hisanori Shiomi, Hiromichi Sonoda, Shigeyuki Naka, Hidetoshi Okabe, Tohru Tani
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] The source of cancer cells in peritoneal metastasis after pancreatic surgery for pancreas cancer2014

    • Author(s)
      村田 聡、竹林克士、塩見尚礼、仲 成幸、赤堀浩也、山本 寛、山口 剛、貝田佐知子、清水智治、園田寛道、太田裕之、目片英治、石田光明、岡部英俊、谷 徹
    • Organizer
      第52回日本癌治療学会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-08-28 – 2014-08-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] Absorption removal of LAP positive cells from human ascites with cancer treatment column2014

    • Author(s)
      小島正継、村田聡、寺本和雄、 目片英治、竹林克士、児玉泰一、PhamMinh Ngoc、小笠原一誠、 谷 徹
    • Organizer
      第69回日本消化器外科学会
    • Place of Presentation
      福島県郡山市
    • Year and Date
      2014-07-16 – 2014-07-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] B7-DC補助刺激を用いた抗腫瘍免疫治療に関する研究2013

    • Author(s)
      小島正継 村田 聡 竹林克士 三宅 亨 北村直美 植木智之 目片英治 谷 徹
    • Organizer
      日本癌免疫学会
    • Place of Presentation
      山口県宇部市ANAクラウンプラザホテル
    • Related Report
      2013 Research-status Report
  • [Presentation] Fusion Protein of Mutant B7-DC and Fc Enhances the Anti-Tumor Immune Effect of GM-CSF Secreting Whole-Cell Vaccine2013

    • Author(s)
      Masatsugu Kojima, Satoshi Murata, Eiji Mekata, Tohru Miyake, Hiromichi Sonoda and Tohru Tani
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜市パシフィコ横浜
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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