Development of oncolytic adenovirus as a new therapeutic agent for treating disseminated cancers

• Project/Area Number: 25460484
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Hyogo Medical University
• Principal Investigator: Kubo Shuji 兵庫医科大学, 医学部, 准教授 (10441320)
• Co-Investigator(Kenkyū-buntansha): YAMANO TOMOKI 兵庫医科大学, 医学部, 講師 (00599318) ; OHYAMA HIDEKI 兵庫医科大学, 医学部, 非常勤講師 (90280685)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 遺伝子治療 / 腫瘍溶解ウイルス / 癌 / ウイルス療法 / 腫瘍溶解アデノウイルス / 癌遺伝子治療 / 腫瘍溶解療法 / インビボ分子イメージング / 悪性中皮腫 / 骨肉腫 / 大腸癌 / 癌標的化

Outline of Final Research Achievements

Disseminated cancers are generally non-curative and novel therapeutic paradigms are urgently required. We developed dual-targeted oncolytic type 5 adenoviruses in which the viral replication was regulated by cancer-specific promoter and the receptor-binding site in the fiber was modified to target CD46 that was highly expressed in most cancer cells. We then examined the anti-tumor effects in various cancer models.

Research Products

• [Journal Article] Combinatorial anti-angiogenic gene therapy in a human malignant mesothelioma model (2015)
  • Author(s): Kubo S, Takagi-Kimura M, Kasahara N
  • Journal Title: Oncology Report Volume: 34 Issue: 2 Pages: 633-638
  • DOI: 10.3892/or.2015.4058
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Oncolytic virotherapy for osteosarcoma using midkine promoter-regulated adenoviruses. (2014)
  • Author(s): Takagi-Kimura M, Yamano T, Tagawa M, Kubo S
  • Journal Title: Cancer Gene Ther. Volume: 21 Issue: 3 Pages: 126-32
  • DOI: 10.1038/cgt.2014.7
  • Peer Reviewed
• [Journal Article] Enhanced antitumor efficacy of fiber-modified, midkine promoter-regulated oncolytic adenovirus in human malignant mesothelioma (2013)
  • Author(s): Takagi-Kimura, M., Yamano, T., Tamamoto, A., Okamura, N., Okamura, H., Hashimoto-Tamaoki, T., Tagawa, M., Kasahara, N. and Kubo, S.
  • Journal Title: Cancer Sci. Volume: 104 Issue: 11 Pages: 1433-1439
  • DOI: 10.1111/cas.12267
  • Peer Reviewed
• [Journal Article] Highly efficient tumor transduction and antitumor efficacy in experimental human malignant mesothelioma using replicating gibbon ape leukemia virus. (2013)
  • Author(s): Kubo S, Takagi-Kimura M, Logg CR, Kasahara N.
  • Journal Title: Cancer Gene Therapy Volume: 20 Issue: 12 Pages: 671-7
  • DOI: 10.1038/cgt.2013.67
  • Peer Reviewed
• [Presentation] Dual-vector prodrug activator gene therapy using two different retroviral replicating vectors (2015)
  • Author(s): Kubo S, Takagi-Kimura M, Logg CR, Hermann K, Kasahara N
  • Organizer: The European Society of Gene and Cell Therapy
  • Place of Presentation: ヘルシンキ（フィンランド）
  • Year and Date: 2015-09-17
  • Int'l Joint Research
• [Presentation] Dual-vector prodrug activator gene therapy using retroviral replicating vectors derived from amphotropic murine leukemia virus and gibbon ape leukemia virus (2015)
  • Author(s): Kubo S, Takagi-Kimura M, Logg CR, Hermann K, Kasahara N
  • Organizer: The American Society of Gene & Cell Therapy
  • Place of Presentation: ニューオーリンズ（米国）
  • Year and Date: 2015-05-13
  • Int'l Joint Research
• [Presentation] 骨肉腫に対する二重制御型アデノウイルスを用いた腫瘍溶解療法 (2014)
  • Author(s): 久保秀司、木村美智、山野智基、田川雅敏
  • Organizer: 第３７回分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-28
• [Presentation] ミッドカインプロモーター制御型アデノウイルスを用いた骨肉腫に対する腫瘍溶解療法 (2014)
  • Author(s): 久保秀司、木村美智、山野智基、玉置知子、田川雅敏
  • Organizer: 人類遺伝学会第５９回大会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] Enhanced transduction and antitumor efficiency of fiber-modified, midkine promoter-regulated oncolytic adenovirus in human malignant mesothelioma (2014)
  • Author(s): Shuji Kubo, Misato Takagi-Kimura and Masatoshi Tagawa
  • Organizer: 12th International Conference of the International Mesothelioma Interest Group
  • Place of Presentation: Cape Town (South Africa)
  • Year and Date: 2014-10-21 – 2014-10-24
• [Presentation] Suicide gene therapy by replicating gibbon ape leukemia virus in an experimental model of human malignant mesothelioma (2014)
  • Author(s): Shuji Kubo, Misato Takagi-Kimura, Christopher R Logg and Noriyuki Kasahara
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] ケモカインCCL21と腫瘍溶解アデノウイルスを用いた新しい癌ワクチン療法の開発 (2014)
  • Author(s): 山野智基、久保秀司、矢野綾、山本 英幸、岡村 春樹、冨田尚裕
  • Organizer: 第52回日本癌治療学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-08-28 – 2014-08-30
• [Presentation] Prodrug activator gene therapy using replicating gibbon ape leukemia virus in an experimental model of human malignant mesothelioma (2014)
  • Author(s): Shuji Kubo, Misato Takagi-Kimura, Christopher R Logg and Noriyuki Kasahara
  • Organizer: 第２０回日本遺伝子治療学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-08-06 – 2014-08-08
• [Presentation] Enhanced transduction and antitumor efficiency of fiber-modified, midkine promoter-regulated oncolytic adenovirus in human malignant mesothelioma (2014)
  • Author(s): Shuji Kubo, Misato Takagi-Kimura, Masatoshi Tagawa
  • Organizer: 11th International Adenovirus Meeting
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2014-07-16 – 2014-07-20
• [Presentation] Highly efficient tumor transduction and antitumor efficacy in experimental human malignant mesothelioma using replicating gibbon ape leukemia virus (2014)
  • Author(s): Shuji Kubo, Misato Takagi-Kimura, Christopher R Logg and Noriyuki Kasahara
  • Organizer: 17th Annual Meeting of the American Society of Gene & Cell Therapy
  • Place of Presentation: Washington DC (USA)
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] 遺伝子治療研究の最近の進歩
  • Author(s): 久保 秀司
  • Organizer: 第42回臨床細胞分子遺伝研究会･第14回関西出生前診療研究会学術集会合同集会
  • Place of Presentation: 西宮
  • Invited
• [Presentation] 増殖型ウイルスを用いた悪性中皮腫に対する自殺遺伝子療法
  • Author(s): 久保 秀司，木村（高木）美智，Logg Christopher R，笠原 典之
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] 二重制御型アデノウイルスを用いた骨肉腫に対する腫瘍溶解療法の開発
  • Author(s): 久保 秀司、木村 美智、玉本 敦子、山野 智基、玉置 知子、笠原 典之、田川 雅敏
  • Organizer: 日本人類遺伝学会第58回大会
  • Place of Presentation: 仙台
• [Presentation] ヘルペスウイルスチミジンキナーゼを用いた癌自殺遺伝子治療を最適化する腫瘍融解ウイルスの開発
  • Author(s): 久保秀司
  • Organizer: 第39回日本応用酵素協会研究発表会
  • Place of Presentation: 大阪
  • Invited
• [Presentation] Dual targeted adenovirus for oncolytic virotherapy in experimental human osteosarcoma
  • Author(s): 久保秀司、木村（高木）美智、山野智基、吉川良恵、江見充、田川雅敏、笠原典之、玉置（橋本）知子
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Midkine Promoter-Driven Oncolytic Adenovirus with Ad35 Fiber Modification Achieves Enhanced Transduction of Human Osteosarcoma Cells.
  • Author(s): Shuji Kubo, Misato Takagi-Kimura, Atsuko Tamamoto, Nobutaka Okamura, Masatoshi Tagawa, Noriyuki Kasahara, Haruki Okamura and Tomoko Hashimoto-Tamaoki
  • Organizer: 第１９回日本遺伝子治療学会学術集会
  • Place of Presentation: 岡山
• [Presentation] Development of Dual Targeted Oncolytic Adenovirus for Human Malignant Mesothelioma.
  • Author(s): Shuji Kubo, Misato Takagi-Kimura, Atsuko Tamamoto, Tomoko Hashimoto-Tamaoki
  • Organizer: 16th Annual Meeting of the American Society of Gene & Cell Therapy
  • Place of Presentation: Salt Lake City, USA