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Development of novel cancer cell vaccine using GM-CSF gene-transuduced IPS cells targeting cancer stem cells

Research Project

Project/Area Number 23790446
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Experimental pathology
Research InstitutionKyushu University

Principal Investigator

INOUE Hiroyuki  九州大学, 生体防御医学研究所, 助教 (80529967)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords癌幹細胞 / iPS細胞 / 腫瘍免疫療法 / GM-CSF / 遺伝子治療 / 肺癌 / 腫瘍免疫 / ワクチン
Research Abstract

Our results of in vitro assays demonstrated that non-transmissible recombinant Sendai virus-mediated mouse GM-CSF gene transfer to iPS (iPS/GM) cells was effective to produce abundant GM-CSF in vitro(200~ng/106cells/24 hrs)and iPS/GM-CSF cells maintained their stemness in terms of morphology and antigenicity as evidenced by the expression levels of SSEA-1,Oct3/4 and alkaline phosphatase similar to those seen in unmodified iPS cells. Our results of in vivo studies using immunocompetent mice demonstrated that mice treated with both prophylactic and therapeutic vaccination using irradiated iPS/GM-CSF (ir.iPS/GM-CSF) cells significantly suppressed the tumor growth of subcutaneously transplanted syngeneic LLC mouse poorly immunogenic lung cancer in the left flank. Of note, during these treatments described above, no serious adverse events were observed with lack of liver and kidney dysfunctions as evidenced by biochemical analysis as well as absence of loss of body weight, suggesting its relative tolerability of use of iPS cells as vaccine cells. Furthermore, in vivo depletion assays showed that the antitumor effect observed in mice treated with ir.iPS/GM-CSF cells was significantly abrogated by depleting CD4+T or CD8+T cells, demonstrating its partial dependence on T cell-mediated cellular antitumor immunity. In conclusion, this is the first report that demonstrated a therapeutic antitumor efficacy of normal fibroblast-derived iPS cell vaccines including iPS/GM cells, providing possible implications that these novel vaccine strategy using iPS cells could induce CSCs associated antigens-specific antitumor immunity and be a promising prophylactic or therapeutic anticancer modality

Report

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

    (6 results)

All 2013 2012 2011

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (5 results)

  • [Journal Article] Coxsackievirus B3 Is an Oncolytic Virus with Immunostimulatory Properties that Is Active Against Lung Adenocarcinoma2012

    • Author(s)
      Miyamoto S, Inoue H, Nakamura T, Yamada M, Sakamoto C, Urata Y, Okazaki T, Marumoto T, Takahashi A, Takayama K, Nakanishi Y, Shimizu H, Tani K
    • Journal Title

      Cancer Research

      Volume: (掲載確定)(印刷中) Issue: 10 Pages: 2609-2621

    • DOI

      10.1158/0008-5472.can-11-3185

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] A novel cancer cell vaccine using induced pluripotent stem cells genetically engineered to produce GM-CSF elicits substantial antitumor immunity in a syngeneic mouse model2013

    • Author(s)
      Hiroyuki Inoue, Ayumi Watanabe,Chika Sakamoto, Megumi Narusawa, Shohei Miyamoto, Makoto Inoue, Koichi Takayama, Mamoru Hasegawa, Yo ichi Nakanishi, and Kenzaburo Tani.
    • Organizer
      第16回米国遺伝子治療学会総会
    • Place of Presentation
      ソルトレークシティ、米国
    • Related Report
      2012 Final Research Report
  • [Presentation] A novel cancer cell vaccine using induced pluripotent stem cells genetically engineered to produce GM-CSF elicits substantial antitumor immunity in a syngeneic mouse model2013

    • Author(s)
      井上博之 (口頭発表)
    • Organizer
      第16回米国遺伝子治療学会
    • Place of Presentation
      ソルトレークシティ
    • Related Report
      2012 Annual Research Report
  • [Presentation] Novel cancer immunotherapy using induced pluripotent stem cells genetically engineered to produce GM-CSF2012

    • Author(s)
      Ayumi Wanatabe, Hiroyuki Inoue, Chika Sakamoto, Megumi Narusawa, Shohei Miyamoto, Makoto Inoue, Keisuke Okita, Koichi Takayama, Mamoru Hasegawa, Yoichi Nakanishi, Shinya Yamanaka, and Kenzaburo Tani
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] Genetically engineered oncolytic Edmonston strain of measles virus harboring the wild-type N, P, L Genes (MV-NPL) effectively target lung cancer stem cells.2012

    • Author(s)
      井上博之
    • Organizer
      American Association of Cancer Research
    • Place of Presentation
      米国 シカゴ
    • Related Report
      2011 Research-status Report
  • [Presentation] Large-Scale Screening Identifies Coxsackievirus B3 (CVB3) as a Promising Oncolytic Virotherapy Agent against Non-Small Cell Lung Cancer2011

    • Author(s)
      井上博之
    • Organizer
      European Society of Gene and Cell Therapy
    • Place of Presentation
      英国 ブライトン
    • Related Report
      2011 Research-status Report

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

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