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Fundamental research on effecitive whole-tumor-cell vaccine

Research Project

Project/Area Number 18K07286
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionHokkaido University

Principal Investigator

WADA Haruka  北海道大学, 遺伝子病制御研究所, 准教授 (70392181)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsがん細胞ワクチン / ワクチン療法 / 腫瘍免疫 / がん免疫
Outline of Final Research Achievements

We have found that a sub-strain of 4T1 (4T1-S), which was discovered by chance, produces a remarkable vaccine effect after X-irradiation. We investigated whether the vaccine response factors could be selected by comparable analysis of gene expression between 4T1-S and its parent strain, 4T1-A, and whether the ineffective vaccine could be converted to an effective vaccine. We found 15 factors that were highly expressed after X-irradiation in the vaccine effective strain. The top three genes were transfected into 4T1-A and the vaccine effect was analyzed, and the effect was enhanced. On the other hand, when the top 3 genes were introduced into CT26 cells with weak vaccine effect and vaccine experiments were performed, complete vaccine effect was observed in all individuals. Therefore, it is clear that the introduction of only the top three genes is effective for the the vaccine effect in some cancer types and individuals.

Academic Significance and Societal Importance of the Research Achievements

がん細胞ワクチンは抗原同定の必要がなく、理論上はすべての患者に有効な可能性のあるワクチンであるため期待は非常に大きかった。しかしがん細胞ワクチンは有効性に乏しく、現在では着目されることはほとんどなくなっている。この状況下、我々はワクチン有効である4T1-S、4T1-Aの発見と解析により、無効ワクチン細胞を有効化する因子を同定した点で学術的意義がある。同定した因子を元に全がん細胞ワクチンを開発できれば、再発予防療法の選択肢が広がることとなる。従ってがん患者にとって福音となり、社会的にも意義がある。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (20 results)

All 2021 2020 2019 2018 Other

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (11 results) (of which Int'l Joint Research: 1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Interleukin-34 Limits the Therapeutic Effects of Immune Checkpoint Blockade2020

    • Author(s)
      Hama Naoki、Kobayashi Takuto、Han Nanumi、Kitagawa Fumihito、Kajihara Nabeel、Otsuka Ryo、Wada Haruka、Lee Hee-kyung、Rhee Hwanseok、Hasegawa Yoshinori、Yagita Hideo、Baghdadi Muhammad、Seino Ken-ichiro
    • Journal Title

      iScience

      Volume: 23 Issue: 10 Pages: 101584-101584

    • DOI

      10.1016/j.isci.2020.101584

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interleukin-34 contributes to poor prognosis in triple-negative breast cancer2020

    • Author(s)
      Kajihara Nabeel、Kitagawa Fumihito、Kobayashi Takuto、Wada Haruka、Otsuka Ryo、Seino Ken-ichiro
    • Journal Title

      Breast Cancer

      Volume: 27 Issue: 6 Pages: 1198-1204

    • DOI

      10.1007/s12282-020-01123-x

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bromodomain-containing protein 4 regulates interleukin-34 expression in mouse ovarian cancer cells2020

    • Author(s)
      Han Nanumi、Anwar Delnur、Hama Naoki、Kobayashi Takuto、Suzuki Hidefumi、Takahashi Hidehisa、Wada Haruka、Otsuka Ryo、Baghdadi Muhammad、Seino Ken-ichiro
    • Journal Title

      Inflammation and Regeneration

      Volume: 40 Issue: 1 Pages: 25-26

    • DOI

      10.1186/s41232-020-00129-4

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Flow cytometric identification and cell-line establishment of macrophages in naked mole-rats.2019

    • Author(s)
      Haruka Wada, Yuhei Shibata, Yurika Abe, Ryo Otsuka, Nanami Eguchi, Yoshimi Kawamura, Kaori Oka, Muhammad Baghdadi, Tatsuya Atsumi, Kyoko Miura, and Ken-ichiro Seino.
    • Journal Title

      Scientific Reports

      Volume: 9 Pages: 17981-17981

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic value of IL-34 in colorectal cancer patients2019

    • Author(s)
      Takuto Kobayashi, Muhammad Baghdadi, Nanumi Han, Tomoki Murata, Naoki Hama, Ryo Otsuka, Haruka Wada, Manabu Shiozawa, Tomoyuki Yokose, Yohei Miyagi, Atsushi Takano, Yataro Daigo, Ken-ichiro Seino.
    • Journal Title

      Immunological Medicine

      Volume: 42 Pages: 169-175

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interleukin-34 expression in ovarian cancer: A possible correlation with disease progression.2019

    • Author(s)
      Hiraku Endo, Naoki Hama, Muhammad Baghdad, Kozo Ishikawa, Ryo Otsuka Haruka Wada, Hiroshi Asano, Daisuke Endo, Yosuke Konno, Tatsuya Kato, Hidemichi Watari, Akiko Tozawa, Nao Suzuki, Tomoyuki Yokose, Atsushi Takano, Hisamori Kato, Yohei Miyagi, Yataro Daigo, Ken-ichiro Seino.
    • Journal Title

      International Immunology

      Volume: 32 Issue: 3 Pages: 175-186

    • DOI

      10.1093/intimm/dxz074

    • NAID

      120006980030

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A role for IL-34 in osteolytic disease of multiple myeloma2019

    • Author(s)
      Baghdadi Muhammad、Ishikawa Kozo、Nakanishi Sayaka
    • Journal Title

      Blood Advances

      Volume: 3 Issue: 4 Pages: 541-551

    • DOI

      10.1182/bloodadvances.2018020008

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 腫瘍開始細胞は炎症環境を形成し免疫細胞を老化させて抗腫瘍応答の低下を導くことで免疫健常個体における腫瘍発生を許容させる2021

    • Author(s)
      和田はるか、清野研一郎
    • Organizer
      日本免疫治療学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Dying but not dead cancer cells exert cell-based cancer vaccine effect2021

    • Author(s)
      Haruka Wada, Nabeel Kajihara, Ken-ichiro Seino
    • Organizer
      日本癌学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 和田はるか. 腫瘍開始細胞は炎症環境を形成し免疫細胞を老化させて抗腫瘍応答の低下を導くことで免疫健常個体における腫瘍発生を許容させる2020

    • Author(s)
      和田はるか、清野研一郎
    • Organizer
      第17回日本免疫治療学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Tumor-initiation via macrophage senescence.2020

    • Author(s)
      Haruka Wada, Toru Kondo, and Ken-ichiro Seino.
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 腫瘍開始細胞は炎症環境を形成し免疫細胞を老化させて抗腫瘍応答の低下を導くことで免疫健常個体における腫瘍発生を許容させる2020

    • Author(s)
      和田はるか、清野研一郎
    • Organizer
      第17回日本免疫治療学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] がん幹細胞はそれ自身が原炎症性細胞であり微小環境に免疫老化及び免疫抑制をもたらすことで健常動物における造腫瘍能を担保する2019

    • Author(s)
      和田はるか、ムハンマドバグダーディー、近藤亨、清野研一郎
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] がん幹細胞はそれ自身が原炎症性細胞であり微小環境に免疫老化及び免疫抑制をもたらすことで健常動物における造腫瘍能を担保する2019

    • Author(s)
      和田はるか、村田智己、大塚亮、森口徹夫、ムハンマドバグダーディー、近藤亨、清野研一郎
    • Organizer
      第23回日本がん免疫学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Tumor-initiating cell induce immuno-hyporesponsiveness following cellular senescence to macrophages2019

    • Author(s)
      Haruka Wada, Baghdadi Muhammad, and Ken-ichiro Seino
    • Organizer
      第38回札幌国際がんシンポジウム
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Tumor-initiating cell induce immuno-hyporesponsiveness following cellular se nescence to macrophages guarantee its tumorigenesis2019

    • Author(s)
      Haruka Wada, Muhammad Baghdadi, and Ken-ichiro Seino
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] がん細胞ワクチンの効果発揮には死細胞でなく「死にゆく」細胞が重要である2018

    • Author(s)
      和田はるか、安宅司、田中睦乃、Baghdadi Muhammad、清野研一郎
    • Organizer
      第22回 日本がん免疫学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Tumor initiating cell in immunocompetent animal defined by immunological features2018

    • Author(s)
      Haruka Wada, Muhammad Baghdadi, Testuo Moriguchi, Toru Kondo, and Ken-ichiro Seino
    • Organizer
      第77回 日本癌学会・総会
    • Related Report
      2018 Research-status Report
  • [Remarks] 北海道大学遺伝子病制御研究所免疫生物分野

    • URL

      https://seinolab.wixsite.com/seinolab/home-1

    • Related Report
      2020 Research-status Report 2019 Research-status Report 2018 Research-status Report
  • [Patent(Industrial Property Rights)] 抗腫瘍組成物及びその製造方法2021

    • Inventor(s)
      清野研一郎、和田はるか
    • Industrial Property Rights Holder
      北海道大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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