Development of oncolytic virotherapy against the refractory gynecologic cancers

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390450
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kanazawa University
• Principal Investigator: INOUE Masaki 金沢大学, 医学系, 教授 (10127186)
• Co-Investigator(Kenkyū-buntansha): KYO Satoru 金沢大学, 医学系, 講師 (50272969) ; TAKAKURA Masahiro 金沢大学, 附属病院, 助教 (20313661) ; NAKAMURA Mitsuhiro 金沢大学, 附属病院, 助教 (50377397)
• Project Period (FY): 2009 – 2011
• Keywords: テロメラーゼ / 腫瘍融解ウイルス / 難治性がん / 腫瘍可視化 / 末梢血中腫瘍細胞 / 非侵襲性癌診断 / 遺伝子診断 / 先進医療

Research Abstract

Despite tremendous development in chemotherapy for refractory gynecologic cancers over the past few decades, the prognosis of the advanced cases is still unsatisfactory, and novel treatment modalities are urgent needed. We developed virotherapy for solid tumors using telomerase-specific replication-selective adenoviruses(OBP-301), in which the human telomerase reverse transcriptase(hTERT) gene promoter has been inserted to direct tumor-specific E1 gene expression. In vitro treatment of Ovarian cancer cell with OBP-301 induced significant cell death in dose-dependent manner, although normal cells showed no significant cell death. Xenograft mouse model of ovarian cancer cells showed the improved survival of mice treated with Telomelysin. These findings support the therapeutic potential of virotherapy using oncolytic virus.
OBP401 in which GFP gene is driven by the CMV-promotor, selectively replicates only in telomerase-positive cells, and therefore may be a tool for cancer screening. We collected a single cell with GFP from blood samples of cervical cancer patients and detected the same HPV-genotype in both CTC and original cancer tissues. This finding suggests that CTC detecting by OBP401 is the useful non-invasive diagnostic way for cancer screening and early detection of recurrent malignant tumors.

Research Products

• [Journal Article] Intraperitoneal administration of telomerase-specific oncolytic adenovirus sensitizes ovarian cancer cells to cisplatin and affect survival in a xenograft model with peritoneal dissemination (2010)
  • Author(s): Takakura M, Nakamura M, Kyo S, Hashimoto M, Mori N, Mizumoto Y, Fujiwara T, Inoue M
  • Journal Title: Cancer Gene Therapy Volume: 17 Pages: 11-19
  • Peer Reviewed
• [Journal Article] Prognostic impact of CD133 expression as a tumor initiating marker in endometrial cancer (2010)
  • Author(s): Nakamura M, Kyo S, Zhang B, MizumotoY, Takakura M, Maida Y, Mori N, Hashimoto M, Ohno S, Inoue M
  • Journal Title: Human pathol Volume: 41 Pages: 1516-1529
  • Peer Reviewed
• [Journal Article] Bone marrow-derived cells from male donors can compose endometrial glands in female transplant recipients (2009)
  • Author(s): Ikoma T, Kyo S, Maida Y, Ozaki S, Takakura M, Nakao S, Inoue M
  • Journal Title: Amer J Obstet Gynecol Volume: 201 Pages: e1-8
  • Peer Reviewed
• [Presentation] 婦人科癌におけるGFP発現テロメラーゼ特異的増殖型アデノウイルスを用いた末梢血中腫瘍細胞の検出 (2011)
  • Author(s): 高倉正博,京哲,中村充宏,毎田佳子,森紀子,水本泰成,保野由紀子,張秀智,井上正樹
  • Organizer: 第70回日本癌学会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-03
• [Presentation] (2011)
  • Author(s): 中村充宏,京哲,高倉正博,毎田佳子,水本泰成,保野由紀子,井上正樹
  • Organizer: 第63回日本産科婦人科学会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2011-08-30
• [Presentation] テロメラーゼ依存性腫瘍融解ウイルスは卵巣癌幹細胞に対して有効である (2010)
  • Author(s): 高倉正博,京哲,中村充宏,毎田佳子,橋本学,森紀子,水本泰成,生駒友美,井上正樹
  • Organizer: 第62回日本産科婦人科学会
  • Place of Presentation: 東京フォーラム(東京都)
  • Year and Date: 2010-04-24
• [Presentation] Virotherapy for platinum-resitant ovarian cancer to overcome CDDP resistance using tumor-specific replication-selective adenovirus. (2009)
  • Author(s): 高倉正博,京哲,中村充宏,橋本学,森紀子,水本泰成,藤原俊義,浦田泰生,井上正樹
  • Organizer: 第68回日本癌学会
  • Place of Presentation: 横浜パシフィコ(神奈川県)
  • Year and Date: 2009-10-01
• [Book] 症例から学ぶ婦人科腫瘍学入門 (2011)
  • Author(s): 井上正樹
  • Total Pages: 1-370
  • Publisher: 永井書店