Development of the Dual fluorescent cytology with tumor-specific viruses for gastrointestinal cancer precision medicine

• Project/Area Number: 16H05416
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Okayama University
• Principal Investigator: FUJIWARA Toshiyoshi 岡山大学, 医歯薬学総合研究科, 教授 (00304303)
• Co-Investigator(Kenkyū-buntansha): 香川 俊輔 岡山大学, 大学病院, 准教授 (00362971) ; 田澤 大 岡山大学, 大学病院, 准教授 (90415513)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2016: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
• Keywords: 癌 / 遺伝子 / 細胞・組織 / 医療・福祉 / トランスレーショナルリサーチ / トランス / トランスレーショナル・リサーチ / ﾄﾗﾝｽﾚｰｼｮﾅﾙ・ﾘｻｰﾁ

Outline of Final Research Achievements

Peritoneal dissemination is the most common form of metastasis in gastrointestinal cancer, and is associated with an extremely poor prognosis. We developed a new approach to visualize floating tumor cells using a green fluorescent protein (GFP)-expressing attenuated adenovirus in which the telomerase promoter regulates viral replication (TelomeScan, OBP-401). Moreover, we used a unique TelomeScan derivative (TelomeScan-F45, OBP-1101) that have a strict replication control function by micro-RNA together with targeting properties through CD46; however, unfortunately, the combination strategy was not able to show the usefulness.

Academic Significance and Societal Importance of the Research Achievements

テロメラーゼ特異的蛍光標識ウイルス製剤TelomeScan（OBP-401）では、EpCAMなど上皮系マーカーを指標としたCellSearchシステムでは検出不能であった、より悪性化して上皮間葉転換（EMT）を生じたがん細胞も標識することができ、鋭敏で高精度な検出感度が確認できた。TelomeScan-F45（OBP-1101）を併用するデュアル体外診断システムの確立は困難であったが、TelomeScanによる臨床的に有用なプラットフォームは構築できたと考える。

Research Products

• [Journal Article] Cancer-associated fibroblasts (CAFs) promote the lymph node metastasis of esophageal squamous cell carcinoma. (2019)
  • Author(s): Kashima H, Noma K, Ohara T, Kato T, Katsura Y, Komoto S, Sato H, Katsube R, Ninomiya T, Tazawa H, Shirakawa Y, Fujiwara T.
  • Journal Title: International Journal of Cancer Volume: 144 Issue: 4 Pages: 828-840
  • DOI: 10.1002/ijc.31953
  • Peer Reviewed
• [Journal Article] Cancer-Associated Fibroblasts Affect Intratumoral CD8+ and FoxP3+ T Cells Via IL6 in the Tumor Microenvironment. (2018)
  • Author(s): Kato T, Noma K, Ohara T, Kashima H, Katsura Y, Sato H, Komoto S, Katsube R, Ninomiya T, Tazawa H, Shirakawa Y, Fujiwara T
  • Journal Title: Clinical Cancer Research Volume: 24 Issue: 19 Pages: 4820-4833
  • DOI: 10.1158/1078-0432.ccr-18-0205
  • Peer Reviewed
• [Journal Article] Integrated fluorescent cytology with nano-biologics in peritoneally disseminated gastric cancer. (2018)
  • Author(s): Watanabe M, Kagawa S, Kuwada K, Hashimoto Y, Shigeyasu K, Ishida M, Sakamoto S, Ito A, Kikuchi S, Kuroda S, Kishimoto H, Tomida S, Yoshida R, Tazawa H, Urata Y, Fujiwara T
  • Journal Title: Cancer Science Volume: 109 Issue: 10 Pages: 3263-3271
  • DOI: 10.1111/cas.13760
  • Peer Reviewed / Open Access
• [Journal Article] OBP-401-GFP telomerase-dependent adenovirus illuminates and kills high-metastatic more effectively than low-metastatic triple-negative breast cancer in vitro. (2017)
  • Author(s): Yano, S., Takehara, K., Kishimoto, H., Tazawa, H., Urata, Y., Kagawa, S., Bouvet, M., Fujiwara, T., Hoffman, R.M
  • Journal Title: Cancer Gene Therapy Volume: 20 Issue: 16 Pages: 45-47
  • DOI: 10.1080/15384101.2016.1249548
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction (2017)
  • Author(s): Yamakawa Yasuaki、Tazawa Hiroshi、Hasei Joe、Osaki Shuhei、Omori Toshinori、Sugiu Kazuhisa、Komatsubara Tadashi、Uotani Kouji、Fujiwara Tomohiro、Yoshida Aki、Kunisada Toshiyuki、Urata Yasuo、Kagawa Shunsuke、Ozaki Toshifumi、Fujiwara Toshiyoshi
  • Journal Title: Cancer Science Volume: 108 Issue: 9 Pages: 1870-1880
  • DOI: 10.1111/cas.13316
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Management of early gastric cancer that meet the indication for radical lymph node dissection following endoscopic resection: a retrospective cohort analysis. (2017)
  • Author(s): Aoyama, K., Kuroda, S., Morihiro, T., Kanaya, N., Kubota, T., Kakiuchi, Y., Kikuchi, S., Nishizaki, M., Kagawa, S., Tazawa, H., Fujiwara, T
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 14177-14177
  • DOI: 10.1038/s41598-017-14717-x
  • Peer Reviewed / Open Access
• [Journal Article] Targeted photodynamic virotherapy armed with a genetically encoded photosensitizer. (2016)
  • Author(s): Takehara K, Kagawa S, Fujiwara T, et al.
  • Journal Title: Molecular Cancer Therapeutics Volume: 15 Issue: 1 Pages: 199-208
  • DOI: 10.1158/1535-7163.mct-15-0344
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Trastuzumab-Based Photoimmunotherapy Integrated with Viral HER2 Transduction Inhibits Peritoneally Disseminated HER2-Negative Cancer (2016)
  • Author(s): Ishida M, Kagawa S, Shimoyama K, Takehara K, Noma K, Tanabe S, Shirakawa Y, Tazawa H, Kobayashi H, Fujiwara T
  • Journal Title: Molecular Cancer Therapeutics Volume: 15 Issue: 3 Pages: 402-411
  • DOI: 10.1158/1535-7163.mct-15-0644
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Ablation of MCL1 expression by virally induced microRNA-29 reverses chemoresistance in human osteosarcomas. (2016)
  • Author(s): Osaki S, Tazawa H, Hasei J, Yamakawa Y, Omori T, Sugiu K, Komatsubara T, Fujiwara T, Sasaki T, Kunisada T,
  • Journal Title: Sci Rep. Volume: 30(6) Issue: 1 Pages: 28953-28953
  • DOI: 10.1038/srep28953
  • Peer Reviewed / Open Access
• [Journal Article] Tumor-specific delivery of biologics by a novel T-cell line HOZOT. (2016)
  • Author(s): Onishi T, Tazawa H, Hashimoto Y, Takeuchi M, Otani T, Nakamura S, Sakurai F, Mizuguchi H, Kishimoto H, Umeda Y, Shirakawa Y, Urata Y, Kagawa S, Fujiwara T.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 38060-38060
  • DOI: 10.1038/srep38060
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant