Telomerase-specific virotherapy for malignant mesothelioma

• Project/Area Number: 19390365
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Okayama University
• Principal Investigator: FUJIWARA Toshiyoshi Okayama University, 医学部・歯学部附属病院, 准教授 (00304303)
• Co-Investigator(Kenkyū-buntansha): KAGAWA Syunsuke 岡山大学, 医学部・歯学部附属病院, 助教 (00362971)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000); Fiscal Year 2008: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2007: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
• Keywords: テロメラーゼ / アデノウイルス / hTERT / ウイルス療法 / 遺伝子治療 / 悪性胸膜中皮腫 / 呼吸器外科学

Research Abstract

悪性胸膜中皮腫は比較的稀な腫瘍であるが、多くの治療の抵抗性と浸潤性の局所進展、極めて不良な平均生存期間などから、何らかの新しい治療戦略の開発が必須と考えられる。本研究では、テロメラーゼ依存性腫瘍融解ウイルス製剤テロメライシンによる治療効果、および蛍光発現同製剤テロメスキャンによる診断機能について検討した。テロメライシンの胸腔内投与は同所性マウスモデルにおいて顕著な抗腫瘍活性を示し、テロメスキャンにて微小胸膜播種巣を可視化することが可能であった。これらのウイルス製剤は、悪性胸膜中皮腫の診断・治療に有用と考えられる。

Research Products

• [Journal Article] A novel antiangiogenic effect for telomerase-specific virotherapy through host immune system (2009)
  • Author(s): Ikeda Y, Kojima T, Kuroda S, Endo Y, Sakai R, Hioki M, Kishimoto H, Uno F, Kagawa S, Watanabe Y, Hashimoto Y, Urata Y, Tanaka N, Fujiwara T
  • Journal Title: J Immunol 182 Pages: 1763-1769
  • Peer Reviewed
• [Journal Article] Telomerase-specific virotherapy in an animal model of human head and neck cancer (2009)
  • Author(s): Nakajima O, Matsunaga A, Ichimaru D, Urata Y, Fujiwara T, Kawakami K
  • Journal Title: Mol Cancer Ther 8 Pages: 171-177
  • Peer Reviewed
• [Journal Article] A novel antiangiogenic effect for telomerase-specific virotherapy teough host immune system. (2009)
  • Author(s): Ikeda, Y.
  • Journal Title: Journal of Immunology 182 Pages: 1763-1769
  • Peer Reviewed
• [Journal Article] Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers (2008)
  • Author(s): Kyo S, Takakura M, Fujiwara T, Inoue M
  • Journal Title: Cancer Sci 99 Pages: 1528-1538
  • NAID: 10024009430
  • Peer Reviewed
• [Journal Article] Virus-mediated oncolysis induces danger signal and stimulates cytotoxic T-lymphocyte activity via proteasome activator upregulation (2008)
  • Author(s): Endo Y, Sakai R, Ouchi M, Onimatsu H, Hioki M, Kagawa S, Uno F, Watanabe Y, Urata Y, Tanaka N, Fujiwara T
  • Journal Title: Oncogene 27 Pages: 2375-2381
  • NAID: 130004903138
  • Peer Reviewed
• [Journal Article] Establishment of Biological and Pharmacokinetic Assays of Telomerase-Specific Replication-Selective Adenovirus (TRAD) (2008)
  • Author(s): Hashimoto Y, Watanabe Y, Shirakiya Y, Uno F, Kagawa S, Kawamura H, Nagai K, Tanaka N, Kumon H, Urata Y, Fujiwara, T
  • Journal Title: Cancer Sci 99 Pages: 385-390
  • Peer Reviewed
• [Journal Article] Combination of oncolytic adenovirotherapy and Bax gene therapy in human cancer xenografted models (2008)
  • Author(s): Hioki M, Kagawa S, Fujiwara T, Sakai R, Kojima T, Watanabe Y, Hashimoto Y, Uno F, Tanaka N, Fujiwara T
  • Journal Title: Potential merits and hurdles for combination therapy. Int J Cancer 122 Pages: 2628-2633
  • Peer Reviewed
• [Journal Article] Autophagy-inducing agents augment the antitumor effect of telomerase-selective oncolytic adenovirus OBP-405 on glioblastoma cells (2008)
  • Author(s): Yokoyama T, Iwado E, Kondo Y, Aoki H, Hayashi Y, Georgescu MM, Sawaya R, Hess KR, Mills GB, Kawamura H, Hashimoto Y, Urata Y, Fujiwara T, Kondo S
  • Journal Title: Gene Ther 15 Pages: 1233-1239
  • Peer Reviewed
• [Journal Article] Virus-mediated oncolysis induces danger signal and stimulates cytotoxic-T-lymphocyte activity via proteasome activator upregulation. (2008)
  • Author(s): Endo, Y.
  • Journal Title: Oncogene 27 Pages: 2375-2381
  • Peer Reviewed
• [Journal Article] Combination of oncolytic adenovirotherapy and Bax gene therapy in human cancer xenografted models. Potential merits and hurdles for combination therapy. (2008)
  • Author(s): Hioki, M.
  • Journal Title: International Journal of Cancer 122 Pages: 2628-2633
  • Peer Reviewed
• [Journal Article] Establishment of Biological and Pharmacokinetic Assays of Telomerase-Specific Replication-Selective Adenovirus (TRAD). (2008)
  • Author(s): Hashimoto, Y.
  • Journal Title: Cancer Science 99 Pages: 385-390
  • Peer Reviewed
• [Journal Article] Virus-mediated oncolysis induces danger signal and stimulates cytotoxic-T-lymphocyte activity via proteasome activator upregulation. (2007)
  • Author(s): Endo, Y.
  • Journal Title: Oncogene (Epub-ahead-of-print)
  • Peer Reviewed
• [Journal Article] Telomerase-specific oncolytic virotherapy for human cancer with the hTERT promoter. (2007)
  • Author(s): Fujiwara, T.
  • Journal Title: Current Cancer Drug Targets 7 Pages: 191-201
  • NAID: 10024559827
• [Presentation] Telomerase-specific oncolytic virotherapy for human cancer (2008)
  • Author(s): Fujiwara, T
  • Organizer: The 2^<nd> Annual Meeting of Korean Society of Gene Therapy
  • Place of Presentation: ソウル
  • Year and Date: 2008-11-28
• [Presentation] Telomerase-specific oncolytic adenoviras for theranostic applications. (2008)
  • Author(s): 藤原俊義
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] Phase I trial of intratumoral administration of telomerase-specific oncolytic adenovirus OBP-301 in patients with advanced solid cancer (2008)
  • Author(s): Fujiwara, T., Tanaka, N., Nemunaitis, J., Senzer, N., Tong, A., Ichimaru, D., Shelby, S., Hashimoto, Y., Kawamura, H., Urata, Y.
  • Organizer: 第14回日本遺伝子治療学会(Plenary Session)
  • Place of Presentation: 札幌
  • Year and Date: 2008-06-12
• [Presentation] Telomerase-specific oncolytic adenovirus for theranostic application (2008)
  • Author(s): 藤原俊義、京哲、水口裕之、浦田泰生、田中紀章
  • Organizer: 第67回日本癌学会学術総会(シンポジウム)
  • Place of Presentation: 名古屋
• [Presentation] Phase I trial of intratumoral administration of OBP-301, a novel telomerase-specific oncolytic virus, in patients with advanced solid cancer : evaluation of biodistribution and immune response (2008)
  • Author(s): Fujiwara, T., Tanaka, N., Nemunaitis, J., Snzer, N., Tong, A., Ichimaru, D., Shelby, S. M., Hashimoto, Y., Kawamura, H., Urata, Y.
  • Organizer: 44th Annual Meeting of the American Society of Clinical Oncology
  • Place of Presentation: シカゴ
• [Presentation] テロメラーゼ活性を標的とした新規ウイルス製剤Telomelysin/TelomeScanの癌診断・治療への応用 (2008)
  • Author(s): 藤原俊義、香川俊輔、宇野太、浦田泰生、田中紀章
  • Organizer: 第108回日本外科学会定期学術集会(ワークショップ)
  • Place of Presentation: 長崎
• [Presentation] Heparanase-assisted oncolytvirotherapy for disseminated malignant pleural mesothelioma in mice (2008)
  • Author(s): Hashimoto, Y., Watanabe, Y., Kojima, T., Kuroda, S., Tanaka, N., Kawamura, H., Nagai, K., Urata, Y., Fujiwara, T.
  • Organizer: 2008 Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: サンディエゴ
• [Presentation] ナノバイオ・ウイルス製剤のがん診断・治療への応用. (2007)
  • Author(s): 藤原俊義、浦田泰生、田中紀章
  • Organizer: 第45回日本癌治療学会総会(シンポジウム)
  • Place of Presentation: 京都
  • Year and Date: 2007-10-26
• [Presentation] In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus expressing GFP gene (2007)
  • Author(s): 藤原俊義、浦田泰生、田中紀章
  • Organizer: 第66回日本癌学会学術総会(シンポジウム)
  • Place of Presentation: 横浜