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Development of virotherapy for osteosarcoma pulmonary metastases using stem cells as carriers

Research Project

Project/Area Number 19K22697
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionHyogo Medical University

Principal Investigator

Kubo Shuji  兵庫医科大学, 医学部, 准教授 (10441320)

Co-Investigator(Kenkyū-buntansha) 山野 智基  兵庫医科大学, 医学部, 非常勤講師 (00599318)
麸谷 博之  兵庫医科大学, 医学部, 教授 (30248140)
中込 隆之  兵庫医科大学, 医学部, 教授 (80434950)
Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords増殖型レトロウイルス / がんウイルス療法 / 骨肉腫 / 肺転移 / 自殺遺伝子療法 / 増殖型レトロウイルスベクター / ウイルス療法
Outline of Research at the Start

申請者らは増殖型レトロウイルスベクター(RRV: Retroviral Replicating Vector)及びこれを用いた癌自殺遺伝子療法を開発し、欧米で第2/3相試験を行なっている。本研究では、本療法の骨肉腫肺転移への適応拡大を目指し、腫瘍に遊走・集積する特性を持つことが知られている間葉系幹細胞(MSC: Mesenchymal Stem Cell)をキャリアとして利用した腫瘍へのRRV輸送法を開発する。

Outline of Final Research Achievements

We have developed a retroviral replicating vector (RRV) that specifically infects and multiplies cancer cells and efficiently spreads and propagates within tumors. By loading a suicide gene onto this RRV, tumor cell death can be induced by administration of a drug precursor, which has shown high infection efficiency and excellent therapeutic efficacy in various tumor models. The results of this study demonstrated that the viral therapy has a high antitumor effect in osteosarcoma models. Furthermore, we have demonstrated a proof-of-principle method to efficiently reach and distribute RRV to cancer cells using mesenchymal stem cells as carriers, taking advantage of their ability to accumulate in cancer cells.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果により、骨肉腫肺転移症例へのRRVを用いた自殺遺伝子療法の適応拡大が期待され、臨床応用可能な実用性の高いウイルス療法開発につながることが期待される。骨肉腫のみならず、播種性癌の患者の予後やQuality of Lifeを大きく改善する可能性がある。

Report

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

    (18 results)

All 2021 2020 2019

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (16 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Assessment of circulating microRNA specific for patients with familial adenomatous polyposis2021

    • Author(s)
      Yamano T, Kubo S, Sonoda E, Kominato T, Kimura K, Yasuhara M, Kataoka K, Son J, Babaya A, Takenaka Y, Matsubara T, Beppu N, Ikeda M
    • Journal Title

      PLoS One

      Volume: 16 Issue: 5 Pages: 250072-250072

    • DOI

      10.1371/journal.pone.0250072

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A patient-derived xenograft and a cell line derived from it form a useful preclinical model for small bowel adenocarcinoma2020

    • Author(s)
      Tomoki Yamano, Shuji Kubo, Naohiro Tomita
    • Journal Title

      Cancer Medicine

      Volume: 00 Issue: 10 Pages: 1-7

    • DOI

      10.1002/cam4.2986

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Suicide gene therapy for ovarian cancer using retroviral replicating vector2021

    • Author(s)
      Sonoda E, Isoda L, Fujino H, Kawabe A, Kasahara N, Kubo S
    • Organizer
      第27回日本遺伝子細胞治療学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 増殖型レトロウイルスを用いた卵巣癌に対する自殺遺伝子治療2021

    • Author(s)
      久保秀司、藤野宏晃、川邉彩音、園田絵観子
    • Organizer
      日本人類遺伝学会第66回大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Suicide gene therapy by retroviral replicating vectors for canine malignancies2021

    • Author(s)
      園田絵観子, 藤野宏晃, 川邉彩音, 寳田徹, 野口俊助, 笠原典之 , 久保秀司
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 骨肉腫に対する増殖型レトロウイルスベクターを用いた細胞死誘導型がんウイルス療法2021

    • Author(s)
      川邉彩音、藤野宏晃、園田絵観子、寳田徹、笠原典之、久保秀司
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Suicide Gene Therapy Using Retroviral Replicating Vectors for Gastric Cancer2021

    • Author(s)
      藤野宏晃、園田絵観子、磯田莉沙、川邉彩音、寳田徹、笠原典之、久保秀司
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Potential Utility Of Retroviral Replicating Vector-Mediated Prodrug Activator Gene Therapy For Human Ovarian Cancer2020

    • Author(s)
      Shuji Kubo, Lisa Isoda, Hiroaki Fujino, Emiko Sonoda, Kosei Hasegawa, Noriyuki Kasahara, Toru Takarada
    • Organizer
      American Society of Gene & Cell Therapy 23rd annual meeting
    • Related Report
      2020 Research-status Report
  • [Presentation] 骨肉腫に対する増殖型レトロウイルスベクターを用いた細胞死誘導型がんウイルス療法2020

    • Author(s)
      久保秀司、磯田 莉沙、藤野 宏晃、園田 絵観子
    • Organizer
      第123回日本小児科学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Usefulness of suicide gene therapy for ovarian cancer using retroviral replicating vector2020

    • Author(s)
      Shuji Kubo, Tomoki Yamano, Kosei Hasegawa
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Suicide Gene Therapy Using Retroviral Replicating Vectors in an Experimental Model of Human Gastric Cancer2020

    • Author(s)
      Shuji Kubo, Hiroaki Fujino, Ayane Kawabe, Noriyuki Kasahara, Emiko Sonoda, and Toru Takarada
    • Organizer
      日本人類遺伝学会第65回大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Mesenchymal Stem Cells as Carriers of Retroviral Replicating Vectors for Cancer Gene Therapy2019

    • Author(s)
      Shuji Kubo, Misato Takagi-Kimura, Lisa Isoda, Hiroaki Fujino, Noriyuki Kasahara
    • Organizer
      第22回米国遺伝子治療学会議(ASGCT 2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of human mesenchymal stem cells as tumor-homing cellular carriers for retroviral replicating vectors2019

    • Author(s)
      Shuji Kubo, Hiroaki Fujino, Takao Morinaga, Masatoshi Tagawa, Noriyuki Kasahara
    • Organizer
      第25回日本遺伝子細胞治療学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 間葉系幹細胞を運搬体として用いた増殖型レトロウイルスベクターの新規デリバリー法の開発2019

    • Author(s)
      久保秀司、藤野 宏晃、笠原典之
    • Organizer
      第26回日本遺伝子診療学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Mesenchymal stem cells as cellular vehicles to deliver retroviral replicating vectors for cancer gene therapy2019

    • Author(s)
      Shuji Kubo, Takao Morinaga, Tomoki Yamano
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Human mesenchymal stem cells as tumor-homing cellular carriers of retroviral replicating vectors for cancer gene therapy2019

    • Author(s)
      Shuji Kubo, Hiroaki Fujino, Noriyuki Kasahara
    • Organizer
      第27回欧州遺伝子細胞治療学会(ESGCT 2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mesenchymal Stem Cells as Carriers of Retroviral Replicating Vectors for Cancer Gene Therapy2019

    • Author(s)
      Shuji Kubo, Misato Takagi-Kimura, Lisa Isoda, Hiroaki Fujino, and Noriyuki Kasahara
    • Organizer
      日本人類遺伝学会第64回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Mesenchymal Stem Cells As Tumor-homing Cellular Carriers For Retroviral Replicating Vectors2019

    • Author(s)
      Hiroaki Fujino, Lisa Isoda, Emiko Sonoda, Noriyuki Kasahara, Shuji Kubo
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report

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Published: 2019-07-04   Modified: 2023-01-30  

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