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Biomarkers for evaluation of clinical activity of VEGFR-targeted vaccines against malignant brain tumor patients

Research Project

Project/Area Number 18K08951
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionKeio University

Principal Investigator

UEDA Ryo  慶應義塾大学, 医学部(信濃町), 講師 (30317143)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords悪性脳腫瘍 / 腫瘍抗原ペプチドワクチン / 脳腫瘍血管新生 / 免疫療法 / バイオマーカー / 難治性脳腫瘍 / 脳腫瘍新生血管 / ペプチドワクチン
Outline of Final Research Achievements

Evaluation of immunological biomarkers may lead to better understanding of the critical immune response indicators that may help to predict clinical responses of cancer immunotherapy. We characterized status of immune cells, cytokines, chemokines, and other immunosuppressive molecules in refractory brain tumor patients who received vaccinations of VEGF receptor (VEGFR)-derived peptides. Peripheral blood samples from patients who demonstrated positive radiologic response or stable disease revealed superior VEGFR-specific CTL reactivity compared to samples from other patients with refractory brain tumors. Plasma IL-8 level was negatively correlated with overall survival. Furthermore, expression of VEGFR1 and VEGFR2 on tumor cells and immunosuppressive tumor-microenvironment were related to the therapeutic efficacy VEGFR-targeted vaccines. These data indicate that these parameters may be potential immune-biomarkers for evaluation of clinical activity of VEGFR-targeted vaccines.

Academic Significance and Societal Importance of the Research Achievements

脳腫瘍血管新生抑制療法とがんワクチン免疫療法という2つの治療要素を併せ持つ悪性脳腫瘍に対する治療はこれまでに行われておらず、本研究により、脳腫瘍微小環境の免疫学的解析や脳腫瘍患者での免疫応答、脳腫瘍血管新生機構の解明など、これまでのがん治療の臨床試験では検証されていなかった知見を、がん免疫療法や腫瘍血管新生抑制療法の改良・開発に向けた基礎研究にフィードバックし得る。また、基礎研究では判明しなかった現象が臨床試験において初めて明らかにされることもある。これらの情報は、今後の免疫的治療法・血管新生抑制療法開発にとって欠かすことができない重要な指針となり、がん医療の発展に寄与する可能性がある。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (8 results)

All 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (5 results)

  • [Journal Article] A VEGF receptor vaccine demonstrates preliminary efficacy in neurofibromatosis type 2.2019

    • Author(s)
      Tamura Ryota, Fujioka Masato, Morimoto Yukina, Ohara Kentaro, Kosugi Kenzo, Oishi Yumiko, Sato Mizuto, Ueda Ryo, Fujiwara Hirokazu, Noji Shinobu, Oishi Naoki, Ogawa Kaoru, Kawakami Yutaka, Ohira Takayuki, Yoshida Kazunari, Toda Masahiro.
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 5758-5768

    • DOI

      10.1038/s41467-019-13640-1

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of VEGF receptors expression on the tumor cells in skull base chordoma.2019

    • Author(s)
      Morimoto Yukina, Tamura Ryota, Ohara Kenta, Kosugi Kenzo, Oishi Yumiko, Kuranari Yuki, Yoshida Kazunari, Toda Masahiro.
    • Journal Title

      Journal of Neurooncology

      Volume: 144 Issue: 1 Pages: 65-77

    • DOI

      10.1007/s11060-019-03221-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma2019

    • Author(s)
      Kikuchi Ryogo、Ueda Ryo、Saito Katsuya、Shibao Shunsuke、Nagashima Hideaki、Tamura Ryota、Morimoto Yukina、Sasaki Hikaru、Noji Shinobu、Kawakami Yutaka、Yoshida Kazunari、Toda Masahiro
    • Journal Title

      Journal of Clinical Medicine

      Volume: 8 Issue: 2 Pages: 263-263

    • DOI

      10.3390/jcm8020263

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 脳腫瘍に対するワクチン療法2019

    • Author(s)
      戸田正博
    • Organizer
      第14回信濃町脳腫瘍セミナー
    • Related Report
      2018 Research-status Report
  • [Presentation] 神経線維腫症2型に対するVEGFRワクチンの臨床試験と今後の展望について2018

    • Author(s)
      戸田正博、田村亮太、大平貴之、吉田一成、藤岡正人、大石直樹、小川 郁
    • Organizer
      第27回日本聴神経腫瘍研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 脳腫瘍に対するワクチン療法の開発2018

    • Author(s)
      戸田正博
    • Organizer
      日本脳神経外科学会 第77回学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 第36回日本脳腫瘍学会学術集会2018

    • Author(s)
      森本佑紀奈、戸田正博、田村亮太、谷口智憲、河上 裕、吉田一成
    • Organizer
      悪性神経膠腫に対するVEGFR 2 ワクチンと抗PD-1抗体併用療法の有効性の検討
    • Related Report
      2018 Research-status Report
  • [Presentation] 神経線維腫症2型に対するVEGF receptor ペプチドワクチンの臨床試験2018

    • Author(s)
      戸田正博、田村亮太、森本佑紀奈、小杉健三、大平貴之、吉田一成
    • Organizer
      第36回日本脳腫瘍学会学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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