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Development of a new treatment method against renal cancer using immune checkpoint inhibitors

Research Project

Project/Area Number 26670703
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Urology
Research InstitutionKyushu University (2015)
Kumamoto University (2014)

Principal Investigator

Eto Masatoshi  九州大学, 医学(系)研究科(研究院), 教授 (90315078)

Co-Investigator(Kenkyū-buntansha) MOTOSHIMA Takanobu  熊本大学, 医学部附属病院, 医員 (60726355)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords癌 / 免疫学
Outline of Final Research Achievements

Recently, molecular targeted drugs including tyrosine kinase inhibitors (TKIs) and mTOR inhibitors have clearly prolonged overall survival of patients with metastatic RCC (mRCC). However, we have already known their limitations in the treatment of mRCC. To improve the antitumor effects, we have established a murine model of renal cancer treatment where a combined treatment with a TKI, sorafenib, and an immune checkpoint inhibitor, anti-CTLA-4 mAb is performed. Two possible mechanisms have been considered. One is a blockade of negative signals via CTLA-4 molecules on T cells by anti-CTLA-4 mAb. The other is an inhibition of immune suppressive genes, such as TGF-beta and IL-10, in myeloid derived suppressor cells (MDSC) by sorafenib. We have also established a murine model of renal cancer treatment where a combination therapy of two immune checkpoint inhibitors, anti-PD1 mAb and anti-CTLA-4 mAb, is performed. A clinical application of this combination therapy is awaited.

Report

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

    (5 results)

All 2016 2015 2014

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (2 results)

  • [Journal Article] CXCL10 and CCL2 mRNA expression in monocytes is inversely correlated with the HLA-DR lower fraction of monocytes in patients with renal cell carcinoma.2016

    • Author(s)
      Motoshima T, Komohara Y, Horlad H, Tsukamoto H, Fujita M, Saito Y, Tanoue K, Kasejima Y, Sugiyama Y, Kawano Y, Nishimura Y, Takeya M, Eto M.
    • Journal Title

      Oncol Lett.

      Volume: 11 Pages: 1911-1916

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Infiltration of tumor-associated macrophages is involved in CD44 expression in clear cell renal cell carcinoma.2016

    • Author(s)
      Ma C, Komohara Y, Ohnishi K, Shimoji T, Kuwahara N, Sakumura Y, Matsuishi K, Fujiwara Y, Motoshima T, Takahashi W, Yamada S, Kitada S, Fujimoto N, Nakayama T, Eto M, Takeya M.
    • Journal Title

      Cancer Sci.

      Volume: Epub Issue: 5 Pages: 700-707

    • DOI

      10.1111/cas.12917

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sorafenib enhances the anti-tumor effect of anti-CTLA-4 antibody by inhibiting myeloid-derived suppressor cells.2015

    • Author(s)
      Motoshima T, Komohara Y, Horlad H, Takeuchi A, Maeda Y, Tanoue K, Kawano Y, Harada M, Takeya M, Eto M
    • Journal Title

      Oncol Rep

      Volume: - Issue: 6 Pages: 2947-2953

    • DOI

      10.3892/or.2015.3893

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] マウス腎癌モデルにおける抗CTLA-4抗体と抗PD-1抗体の併用療法による抗腫瘍効果についての検討.2014

    • Author(s)
      元島崇信、菰原義弘、哈斯塔、河野吉昭、竹屋元裕、江藤正俊
    • Organizer
      第73回 日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] マウス腎癌モデルにおける抗CTLA-4抗体と抗PD-1抗体の併用療法による抗腫瘍効果についての検討2014

    • Author(s)
      元島崇信、菰原義弘、哈斯塔、河野吉昭、竹屋元裕、江藤正俊
    • Organizer
      第45回 腎癌研究会
    • Place of Presentation
      品川インターシティホテル
    • Year and Date
      2014-07-20
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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