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Anti-tumor immunotherapy targeting a cancer stem cell-specific protein for small cell lung cancer

Research Project

Project/Area Number 23591141
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNiigata University

Principal Investigator

KAGAMU HIROSHI  新潟大学, 医歯学系, 講師 (30418686)

Co-Investigator(Kenkyū-buntansha) NAKATA Ko  新潟大学, 医歯学総合病院, 教授 (80207802)
TSUCHIDA Masanori  新潟大学, 医歯学系, 教授 (60293221)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsDDX3X / 小細胞肺癌 / 抗腫瘍免疫療法 / メラノーマ / CD4+ T細胞 / 国債情報交換 / 国際情報交流
Research Abstract

[Background] Small cell lung cancer (SCLC) possesses high tendency to disseminate. However, SCLC patients with paraneoplastic syndrome mediated by immunity against onconeural antigens remain in limited-stage disease (LD) without distant metastases. We previously reported that DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked (DDX3X) is an immunogenic protein preferentially expressed in CD133+ murine melanoma cells exhibiting biological CSC features. [Results] Five of 15 LD-SCLC patients possessed DDX3X-responsive effector T cells. CD4+ effector T cells obtained from peripheral blood of 5 LD-SCLC secreted significantly more IFNgamma upon DDX3X antigen stimulation in the presence of CD11c+ autologous dendritic cells. effector T cells from one LD-SCLC patient responded to DDX3X. In contrast, effector T cells obtained from ED-SCLC patients or healthy volunteers never responded to DDX3X. DDX3X-primed CD4+ T cells mediated potent antitumor therapeutic efficacy in murine models.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (15 results)

All 2013 2012 2011

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (6 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is an immunogenic target of cancer stem cells2013

    • Author(s)
      Koshio, J. Kagamu, H. Nozaki, K. Saida, Y. Tanaka, T. Shoji, S. Igarashi, N. Miura, S. Okajima, M. Watanabe, S. Yoshizawa, H. Narita, I.
    • Journal Title

      Cancer Immunol Immunother

      Volume: 62 Issue: 10 Pages: 1619-28

    • DOI

      10.1007/s00262-013-1467-x

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] mTOR inhibitors control erlotinib-resistance of EGFR mutant lung cancer cells triggered by HGF.2013

    • Author(s)
      Ishikawa D, Yano S, et al.
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 5 Pages: e62104-e62104

    • DOI

      10.1371/journal.pone.0062104

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-17 eliminates therapeutic effects of oral tolerance in murine airway allergic inflammation.2012

    • Author(s)
      Kawakami, H., Koya, T., Kagamu, H., Kimura, Y., Sakamoto, H., Yamabayashi, C., Furukawa, T., Sakagami, T., Miyabayashi, T., Hasegawa, T., Suzuki, E. and Narita, I.
    • Journal Title

      Clin Exp Allergy

      Volume: 42 Issue: 6 Pages: 946-957

    • DOI

      10.1111/j.1365-2222.2012.04006.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epitope diversification driven by non-tumor epitope-specific Th1 and Th17 mediates potent antitumor reactivity.2012

    • Author(s)
      Ichikawa, K., Kagamu, H., Koyama, K., Miyabayashi, T., Koshio, J., Miura, S., Watanabe, S., Yoshizawa, H. and Narita, I.
    • Journal Title

      Vaccine

      Volume: 30 Issue: 43 Pages: 6190-7

    • DOI

      10.1016/j.vaccine.2012.07.060

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Depletion of radio-resistant regulatory T cells enhances antitumor immunity during recovery from lymphopenia.2012

    • Author(s)
      Baba, J., Watanabe, S., Saida, Y., Tanaka, T., Miyabayashi, T., Koshio, J., Ichikawa, K., Nozaki, K., Miura, S., Tanaka, H., Tanaka, J., Kagamu, H., Yoshizawa, H., Nakata, K. and Narita, I.
    • Journal Title

      Blood

      Volume: 120 Issue: 12 Pages: 2417-27

    • DOI

      10.1182/blood-2012-02-411124

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Vaccination with CD133(+) melanoma induces specific Th17 and Th1 cell-mediated antitumor reactivity against parental tumor2011

    • Author(s)
      Miyabayashi T, Yoshizawa H, et al
    • Journal Title

      Cancer Immunol Immunother

      Volume: 11 Issue: 11 Pages: 1597-608

    • DOI

      10.1007/s00262-011-1063-x

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis2011

    • Author(s)
      Watanabe, S. Tanaka, J. Ota, T. Kondo, R. Tanaka, H. Kagamu, H. Ichikawa, K. Koshio, J. Baba, J. Miyabayashi, T. Narita, I. Yoshizawa, H.
    • Journal Title

      BMC Cancer

      Volume: 11 Issue: 1 Pages: 1-1

    • DOI

      10.1186/1471-2407-11-1

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked plays oncogenic roles to induce cancer stem cell-like properties2013

    • Author(s)
      Koichiro Nozaki, Hiroshi Kagamu, Satoshi Shoji, Natsue Ikarashi, Masaaki Okajima, Satoru Miura, Satoshi Watanabe, Hirohisa Yoshizawa, Ichiei Narita
    • Organizer
      American Association for Cancer Research
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] DDX3X plays a critical role in a novel EGFR-TKI resistance mechanism correlating with CSC-like properties.2013

    • Author(s)
      Koichiro Nozaki, Hiroshi Kagamu, Jun Koshio, Kosuke Ichikawa, Yu Saida, Tomohiro Tanaka, Satoshi Watanabe, Hirohisa Yoshizawa, and Ichiei Narita
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked plays an oncogenic roles to induce cancer stem cell-like properties2012

    • Author(s)
      Koichiro Nozaki1, Hiroshi Kagamu1, Yu Saida1, Tomohiro Tanaka1, Satoshi Watanabe2, Hirohisa Yoshizawa2, and Ichiei Narita1
    • Organizer
      European Society for Medical Oncology
    • Place of Presentation
      Vienna, Austria
    • Related Report
      2012 Research-status Report
  • [Presentation] Oncogenic roles of DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked2012

    • Author(s)
      Koichiro Nozaki1, Hiroshi Kagamu1, Yu Saida1, Tomohiro Tanaka1, Satoshi Watanabe2, Hirohisa Yoshizawa2, and Ichiei Narita1
    • Organizer
      日本癌学会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is a CD133+ tumor-specific protein and induces antitumor immunity2011

    • Author(s)
      Jun Koshio1, Hiroshi Kagamu1, et al.
    • Organizer
      AACR
    • Place of Presentation
      Orange County convention center (Orland, Florida, USA)
    • Related Report
      2011 Research-status Report
  • [Presentation] DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is a CD133+ tumor-specific protein and induces antitumor immunity2011

    • Author(s)
      Jun Koshio1, Hiroshi Kagamu1, et al.
    • Organizer
      日本癌学会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Related Report
      2011 Research-status Report
  • [Patent(Industrial Property Rights)] 癌幹細胞に発現する分子をターゲットとした癌を診断、治療する方法2013

    • Inventor(s)
      各務博、成田一衛、林隆史、後藤義博
    • Industrial Property Rights Holder
      各務博、成田一衛、林隆史、後藤義博
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-09-03
    • Related Report
      2013 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 癌幹細胞に発現する分子をターゲットとした癌を診断、治療する方法2012

    • Inventor(s)
      各務博、成田一衛、林隆史、後藤義博
    • Industrial Property Rights Holder
      各務博、成田一衛、林隆史、後藤義博
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-09-04
    • Acquisition Date
      2013-09-03
    • Related Report
      2013 Final Research Report
    • Overseas

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Published: 2011-08-05   Modified: 2019-07-29  

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