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Development of intravesical human gdT cell based immunotherapy against urinary bladder cancer cell

Research Project

Project/Area Number 15K10604
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Nakanishi Hiyoyuki  京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (40398376)

Co-Investigator(Kenkyū-buntansha) 浮村 理  京都府立医科大学, 医学(系)研究科(研究院), 教授 (70275220)
芦原 英司  京都薬科大学, 薬学部, 教授 (70275197)
中村 晃和  京都府立医科大学, 医学(系)研究科(研究院), 客員教授 (10381964)
上田 崇  京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (50601598)
三木 恒治  京都府立医科大学, 医学(系)研究科(研究院), 特任教授 (10243239)
Research Collaborator SHIMIZU TERUKI  松下記念病院, 泌尿器科, 医長
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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsγδT細胞 / 膀胱癌 / 膀胱注入療法 / 正所性膀胱癌モデル / γδT細胞 / MICA/B / 複合免疫療法 / 膀胱癌注入療法
Outline of Final Research Achievements

Human γδT cell immunotherapy has shown promising results in clinical trials; however, its antitumor efficacy is limited, including results in solid tumors. Ex-vivo expanded γδT cells show potent cytotoxicity against various types of cancer cells in a major histocompatibility complex (MHC)-unrestricted manner. Although several clinical trials of systemic cancer immunotherapy using γδT cells have been conducted, the results are unsatisfactory. The effector (γδT cell)-to-target (tumor cell) (E/T) ratio is an important factor determining cytotoxicity.A bladder instillation approach was used to increase the E/T ratio. The efficacy of γδT cell immunotherapy was examined in an orthotopic xenograft model. In Vivo Imaging System (IVIS) analysis revealed the potent cytotoxicity of weekly intravesical administration of γδT cells.The results indicate that the bladder infusion approach may be clinically applicable and could have beneficial effects in refractory bladder cancer.

Report

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

    (10 results)

All 2018 2017 2016 2015

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Low dose gemcitabine increases the cytotoxicity of human Vγ9Vδ2 T cells in bladder cancer cells in vitro and in an orthotopic xenograft model2018

    • Author(s)
      Teruki Shimizu et al
    • Journal Title

      OncoImmunology

      Volume: Volume 7, 2018 - Issue 5 Issue: 5 Pages: e1424671-e1424671

    • DOI

      10.1080/2162402x.2018.1424671

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isopentenyl pyrophosphate secreted from zoledronate-stimulated myeloma cells, activates the chemotaxis of γδT cells.2015

    • Author(s)
      Eishi Ashihara, Tatsuya Munaka, Shinya Kimura, Saori Nakagawa, Yoko Nakagawa, Masaki Kanai, Hideyo Hirai, Hirohisa Abe, Takashi Miida, Susumu Yamato, Shuichi Shoji, Taira Maekawa
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 463 Issue: 4 Pages: 650-655

    • DOI

      10.1016/j.bbrc.2015.05.118

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 難治性膀胱癌に対するγδT細胞と標準治療薬併用による複合免疫療法の開発2018

    • Author(s)
      清水輝記、宮下雅亜、本郷文弥、浮村理、芦原英司
    • Organizer
      第27回泌尿器科分子細胞研究会 (東京)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Low dose gemcitabine increases the cytotoxicity of human γδT cell in in vitro and in an orthotopic xenograft model in bladder cancer2018

    • Author(s)
      Shimizu T, Miyashita M, Tomogane M, Ukimura O, Ashihara E
    • Organizer
      33rd European Association of Urology (EAU) Congress (Copenhagen)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Combined use of standard anticancer agents increases the cytotoxicity of human γδT cell in in vitro and in vivo in bladder cancer2018

    • Author(s)
      Teruki Shimizu, Mako Tomogane, Masatsugu Miyashita, Osamu Ukimura, Eishi Ashihara
    • Organizer
      第106回日本泌尿器科学会総会. (京都)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of intravesical human γδ T therapy against refractory bladder cancer and human γδ T based chemoimmunotherapy.2017

    • Author(s)
      Teruki Shimizu
    • Organizer
      第105回日本泌尿器科学会総会
    • Place of Presentation
      鹿児島城山観光ホテル
    • Year and Date
      2017-04-21
    • Related Report
      2016 Research-status Report
  • [Presentation] 難治性膀胱癌に対するγδT細胞を用いた複合免疫療法の開発、gemcitabine (GEM)併用による相乗効果の検討2017

    • Author(s)
      清水輝記、友金眞光、宮下雅亜、浮村 理、芦原英司
    • Organizer
      第47回京阪泌尿器腫瘍セミナー(大阪)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 難治性膀胱癌に対するγδT細胞を用いた新規膀胱注入療法の開発2017

    • Author(s)
      清水輝記、友金眞光、宮下雅亜、佐野友亮、清水大器、戸田侑紀、藤原敦子、高田和幸、浮村 理、芦原英司
    • Organizer
      第7回4大学連携研究フォーラム(京都)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 2 Chemotherapeutic agent pretreatment enhances the human γδT cell cytotoxicity against urinary bladder cancer cells.2016

    • Author(s)
      Teruki Shimizu
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] γδTcells have cytotoxicity against cancer cells regardless of PD-L1 expression in cancer cells.2016

    • Author(s)
      Mako Tomogane
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report

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

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