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Development of novel immune cell therapy combined with immune checkpoint inhibitors

Research Project

Project/Area Number 26460914
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General internal medicine(including psychosomatic medicine)
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Ishikawa Takeshi  京都府立医科大学, 医学(系)研究科(研究院), 講師 (90372846)

Co-Investigator(Kenkyū-buntansha) 岡山 哲也  京都府立医科大学, 医学(系)研究科(研究院), 助教 (30636535)
坂元 直行  公益財団法人ルイ・パストゥール医学研究センター, その他部局等, 研究員(移行) (40547981)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords免疫チェックポイント阻害剤 / がん免疫療法 / 細胞移入療法
Outline of Final Research Achievements

Although immune checkpoint inhibitors (ICI) improve clinical outcomes in numerous malignancies, the achievement of durable response is rare in many cancers and the anti-tumor effects of ICI cannot be expected in patients with an absence of CTLs in tumors. Development of new multidisciplinary treatment using immunotherapies and conventional treatment including chemotherapy is necessary for improving treatment outcomes of ICI. This study indicated that adoptive T-cell therapy combined with ICI potentiate the antitumor effects, partially resulting from Th1 polarization and the reduction of the number of Foxp3(+) cells in the tumor. In the study on the effect of anticancer drugs on immune checkpoint molecules, we observed that PD-L1 surface protein expression was enhanced, when pancreatic cancer cell lines were stimulated by anticancer drugs. We believe that our results of the present study will contribute to the development of new immune-based combination therapies.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (17 results)

All 2017 2016 2015 2014

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Acknowledgement Compliant: 4 results,  Open Access: 3 results) Presentation (12 results) (of which Int'l Joint Research: 4 results) Book (1 results)

  • [Journal Article] The JAK/STAT pathway is involved in the upregulation of PD-L1 expression in pancreatic cancer cell lines.2017

    • Author(s)
      Doi T, Ishikawa T, Okayama T, Oka K, Mizushima K, Yasuda T, Sakamoto N, Katada K, Kamada K, Uchiyama K, Handa O, Takagi T, Naito Y, Itoh Y
    • Journal Title

      Oncology report

      Volume: 37 Issue: 3 Pages: 1545-1554

    • DOI

      10.3892/or.2017.5399

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cytotoxic T lymphocyte-associated antigen 4 inhibition increases the antitumor activity of adoptive T-cell therapy when carried out with naïve rather than differentiated T cells.2015

    • Author(s)
      Ishikawa T, Adachi S, Okayama T, Kokura S
    • Journal Title

      Oncol Rep.

      Volume: 33(5) Issue: 5 Pages: 2545-2552

    • DOI

      10.3892/or.2015.3815

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Tumor inoculation site affects the development of cancer cachexia and muscle wasting.2015

    • Author(s)
      Matsuyama T, Ishikawa T, Okayama T, Oka K, Adachi S, Mizushima K, Kimura R, Okajima M, Sakai H, Sakamoto N, Katada K, Kamada K, Uchiyama K, Handa O, Takagi T, Kokura S, Naito Y, Itoh Y.
    • Journal Title

      Int J Cancer.

      Volume: Dec 1;137(11) Issue: 11 Pages: 2558-65

    • DOI

      10.1002/ijc.29620

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer.2015

    • Author(s)
      Sakamoto N, Ishikawa T, Kokura S, Okayama T, Oka K, Ideno M, Sakai F, Kato A, Tanabe M, Enoki T, Mineno J, Naito Y, Itoh Y, Yoshikawa T.
    • Journal Title

      J Transl Med.

      Volume: Aug 25;13 Issue: 1 Pages: 277-277

    • DOI

      10.1186/s12967-015-0632-8

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 抗癌刺激はJAK/STAT経路を介し、膵癌細胞株のPD-L1発現を亢進する2016

    • Author(s)
      土井俊文、石川剛、岡山哲也、他
    • Organizer
      第20回日本がん免疫学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2016-07-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] The expression of PD-L1 on human and murine pancreatic ductal adenocarcinoma is enhanced by anticancer agents via the JAK/STAT pathway.2016

    • Author(s)
      Doi T, Ishikawa T, Yasuda T, et al
    • Organizer
      the 107th Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      New Orleans, Louisiana, USA
    • Year and Date
      2016-04-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 抗癌剤は膵癌細胞株のPD-L1発現を増強し、温熱処理は抗癌剤誘導PD-L1発現を抑制する2015

    • Author(s)
      土井俊文、石川剛、岡要、安田知代、岡山哲也、坂元直行、鎌田和浩、堅田和弘、内山和彦、半田修、高木智久、内藤裕二、伊藤義人
    • Organizer
      第28回日本バイオセラピィ学会学術集会総会
    • Place of Presentation
      川越
    • Year and Date
      2015-12-03
    • Related Report
      2015 Research-status Report
  • [Presentation] The influence of anticancer agents and heat treatment on PD-L1 expression on pancreatic cancer cell lines2015

    • Author(s)
      岡要、土井俊文、石川剛、岡山哲也、安田知代、坂元直行、堅田和弘、鎌田和浩、内山和彦、半田修、高木智久、内藤裕二、伊藤義人
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
  • [Presentation] A novel expansion method for functional natural killer cells and its clinical applicatio.2015

    • Author(s)
      Takeshi Ishikawa, Naoyuki Sakamoto, Tetsuya Okayama , Satoshi Kokura, Mitsuko Ideno, Akiko Kato, Tatsuji Enoki,, Masanari Kitagawa, Junichi Mineno, Tomoyo Yasuda, Toshifumi Doi, Yuji Naito, Yoshito Itoh, Toshikazu Yoshikawa
    • Organizer
      106th Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      Philadelphia
    • Year and Date
      2015-04-21
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] The influence of anticancer agents and hyperthermia on PD-L1 expression on human and murine pancreatic cancer cell lines.2015

    • Author(s)
      Toshifumi Doi, Tetsuya Okayama, Takeshi Ishikawa, Kaname Oka, Naoyuki Sakamoto, Yuji Naito, Yoshito Itoh
    • Organizer
      106th Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      Philadelphia
    • Year and Date
      2015-04-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Elevated levels of plasma VEGF associated with the attenuation of whole blood IFN-γ production and QOL impairment in patients with advanced gastric cancer.2015

    • Author(s)
      Naoyuki Sakamoto, Takeshi Ishikawa, Toshihumi Doi, Tetsuya Okayama, Hideyuki Konishi, Satoshi Kokura, Yuji Naito, Yoshito Ito, Toshikazu Yoshikawa
    • Organizer
      106th Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      Philadelphia
    • Year and Date
      2015-04-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] NK細胞を用いた胃癌に対するTrastuzumabの抗腫瘍効果増強についての検討2014

    • Author(s)
      岡山 哲也, 石川 剛, 坂元 直行, 古倉 聡, 出野 美津子, 加藤 彰子, 榎 竜嗣, 峰野 純一, 吉田 直久, 鎌田 和浩, 堅田 和弘, 内山 和彦, 半田 修, 高木 智久, 小西 英幸, 八木 信明, 内藤 裕二, 吉川 敏一, 伊藤 義人
    • Organizer
      第54回日本消化器病学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2014-10-24
    • Related Report
      2014 Research-status Report
  • [Presentation] CTLA-4阻害薬は分化型よりも未分化型T細胞を用いた養子免疫療法との併用においてより強い効果を発揮する2014

    • Author(s)
      石川 剛、足立 聡子、岡山 哲也、岡 要、土井 俊文、坂元 直行、鎌田 和浩、内山 和彦、半田 修、高木 智久、古倉 聡、内藤 裕二、伊藤 義人
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25
    • Related Report
      2014 Research-status Report
  • [Presentation] 行・再発消化器がんを対象とした新規培養法を用いた高純度NK細胞療法の第I相臨床試2014

    • Author(s)
      坂元 直行、石川 剛、岡山 哲也、出野 美津子、榎 竜嗣、峰野 純一、古倉 聡、内藤 裕二、伊藤 義人、吉川 敏一
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25
    • Related Report
      2014 Research-status Report
  • [Presentation] Advantages and clinical application of fibronectin CH296-stimulated T cells in cancer immunotherapy2014

    • Author(s)
      Ishikawa T, Kokura S, Okayama T, Sakamoto N, Ideno M, Muraki N, Kato A, Enoki T, Mineno J, Naito Y, Itoh Y, Yoshikawa T.
    • Organizer
      105th Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      San Diego, CA
    • Year and Date
      2014-04-07
    • Related Report
      2014 Research-status Report
  • [Presentation] High purity and activity NK cells therapy in patients with advanced gastrointestinal cancer: Phase I study2014

    • Author(s)
      Okayama T, Kokura S, Ishikawa T, Sakamoto N, Ideno M, Sakai F, Kato A, Enoki T, Mineno J, Konishi H, Naito Y, Itoh Y, Yoshikawa T.
    • Organizer
      105th Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      San Diego, CA
    • Year and Date
      2014-04-07
    • Related Report
      2014 Research-status Report
  • [Book] Hyperthermia Combined with Chemotherapy: Pancreatic Cancer. Hyperthermic Oncology from Bench to Bedside.2016

    • Author(s)
      Takeshi Ishikawa
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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