Carrier cell mediated ovarian cancer specific gene therapy

• Project/Area Number: 15591754
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Ehime University
• Principal Investigator: HAMADA Katsuyuki Ehime University, University hospital, Lecturer, 医学部附属病院, 講師 (90172973)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: Ovarian cancer / Oncolytic adenovirus / IAI.3B / Promoter / Carrier cell / Anti-adenovirus antibody / 293 cell / A549 cell / 坑アデノウイルス抗体

Research Abstract

We constructed an oncolytic adenovirus, AdE3-IAI.3B that was introduced ovarian cancer specific IAI.3B promoter, and showed the effect of the growth inhibition in the ovarian cancer cell proliferation in vitro and in vivo (Cancer Research, 2003). The treatment by AdE3-IAI.3B is assumed the problem that all tumors relapses in 2-3 weeks further even if tumor reduction is temporarily done on about 30 days after the treatment. This is confirmed not only in the animal experiment but also in the clinical trial by using other oncolytic vectors. It is guessed that it is a cause that vector rapidly shifts to the whole body from the tumor, because the stagnation rate of vector in the tumor is few, and the stagnation time in the tumor is short. After AdE3-IAI.3B had been infected to 293 and A549 cells that had been known as an adenoviral production cell so far as a carrier cell and these carrier cells were adminstered to the nude mouse subcutaneous tumor model of ovarian cancer PA-1 and RMG-1 cel l that the IAI.3B promoter is high, both tumors completely disappeared and did not relapsed. On the other hand, the HEY cell tumor, whose adenoviral receptor is fewer than these cells, disappeared and the relapse was not admitted when both were used together, though the tumor did not disappear after the single cell treatment by 293 or A549 cells infected with AdE3-IAI.3B. It is well known that the second challenge of adenoviral vectors is completely blocked by the anti-adenoviral antibody production. However, the second challenge of adenovirus succeeded by using AdE3-IAI.3B infected 293 or A549 carrier cell. This restoration of the second adenoviral infection was completely blocked by 0. 4 um millicell membrane chamber and 50% blocked by 12 um millicell memebrane chamber. This was due to the infection achievement by direct carrier cell to target cell contact and carrier cell fragment to target cell contact. This infection style of oncoloytic adenovirus infected carrier cell was confirmed by the electron microscope.

Research Products

• [Journal Article] Midkine promoter-based conditionally replicative adenovirus for malignant glioma therapy. (2004)
  • Author(s): Kohno, S., Nakagawa, K., Hamada, K., Harada, H., Yamasaki, K.et al.
  • Journal Title: Oncology Report 12 Pages: 73-78
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A Cox-2 Promoter-Based Replication-Selective Adenoviral Vector to Target the Cox-2-Expressing Human Bladder Cancer Cells. (2004)
  • Author(s): Shirakawa, T., Hamada, K.et al.
  • Journal Title: Clinical Cancer Research 10 Pages: 4342-4348
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Introduction of p16 INK4a inhibits telomerase activity through transcriptional suppression of human telomerase reverse transcriptase expression in human gliomas. (2004)
  • Author(s): Saito, M., Nakagawa, K., Hamada, K.et al.
  • Journal Title: International Journal of Oncology 24 Pages: 1213-1220
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Midkine promoter-driven suicide gene expression and -mediated adenovirus replication produced cytotoxic effects to immortalized and tumor cells. (2004)
  • Author(s): Yu, L., Hamada, K.et al.
  • Journal Title: Eurorpean Journal of Cancer 40 Pages: 1787-1794
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Midkine promoter-based conditionally replicative adenovirus for malignant glioma therapy. (2004)
  • Author(s): Kohno, S., Nakagawa, K., Hamada, K., Harada, H., Yamasaki, K., Hashimoto, K., Tagawa, M., Nagato, S., Furukawa, K., Ohnishi, T.
  • Journal Title: Oncol Rep. 12 Pages: 73-78
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A Cox-2 Promoter-Based Replication-selective adenoviral vector to target the Cox-2-expressing human bladder cancer cells. (2004)
  • Author(s): Shirakawa, T., Hamada, K., Zhang, Z., Okada, H., Tagawa, T., Kamidono, S., Kawabata, M., Gotoh, A.
  • Journal Title: Clin.Cancer Res. 10 Pages: 4342-4348
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Introduction of p16 INK4a inhibits telomerase activity through transcriptional suppression of human telomerase reverse transcriptase expression in human gliomas. (2004)
  • Author(s): Saito, M., Nakagawa, K., Hamada, K., H i rose, S., Harada, H., Kohno, S., Nagato, S., Ohnishi, T.
  • Journal Title: International Journal of Oncology 24 Pages: 1213-1220
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Midkine promoter-driven suicide gene expression and -mediated adenovirus replication produced cytotoxic effects to immortalized and tumour cells. (2004)
  • Author(s): Yu, L., Hamada, K., Namba, M., Kadomatsu, K., Muramatsu, T., Matsubara, S., Tagawa, M.
  • Journal Title: Eur J Cancer 40 Pages: 1787-1794
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Midkine promoter-driven suicide gene expression and -mediated adenovirus replication produced cytotoxic effects to immortalized and tumour cells. (2004)
  • Author(s): Yu, L., Hamada, K.et al.
  • Journal Title: European Journal of Cancer 40 Pages: 1787-1794
• [Journal Article] Introduction of wild-type p53 enhances thrombospondin-1 expression in human glioma cells. (2003)
  • Author(s): Harada, H., Nakagawa, K., Saito, M.et al.
  • Journal Title: Cancer Letters 191 Pages: 109-119
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of the human IAI.3B promoter element and its use in the construction of a replication-selective adenovirus for ovarian cancer therapy. (2003)
  • Author(s): Hamada, K., Kohno, S.et al.
  • Journal Title: Cancer Research 63 Pages: 2506-2512
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Introduction of wild-type p53 enhances thrombospondin-1 expression in human glioma cells. (2003)
  • Author(s): Harada, H., Nakagawa, K., Saito, M., Kohno, S., Nagato, S., Furukawa, K., Kumon, Y., Hamada, K., Ohnishi, T.
  • Journal Title: Cancer Letters 191 Pages: 109-119
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of the human IAl.3B promoter element and its use in the construction of a replication-selective adenovirus for ovarian cancer therapy. (2003)
  • Author(s): Hamada, K., Kohno, S., Iwamoto, M., Yokota, H., Okada, M., Tagawa, M., Hirose, S., Yamasaki, K., Shirakata, Y., Hashimoto, K., Ito, M.
  • Journal Title: Cancer Research 63 Pages: 2506-2512
  • Description: 「研究成果報告書概要(欧文)」より
• [Patent(Industrial Property Rights)] 癌遺伝子治療薬 (2003)
  • Inventor(s): 濱田 雄行
  • Industrial Property Rights Holder: 新産業創造研究機構
  • Filing Date: 2003-10-15
  • Description: 「研究成果報告書概要(和文)」より
• [Patent(Industrial Property Rights)] 癌遺伝子治療薬 (2003)
  • Inventor(s): 濱田 雄行
  • Industrial Property Rights Holder: 新産業創造研究機構
  • Filing Date: 2003-10-15
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hamada, K. et al.: "Identification of the human IAI.3B promoter element and its use in the construction of a replication selective adenovirus for ovarian cancer therapy"Cancer Research. 632. 2506-2512 (2003)
• [Publications] Yu, L.et al.: "Insertion of an exogenous promoter in the E1A regulatory region of adenovirus does not disturbe viral replication despite reduced E1A transcrition"Cancer Letters. 191. 109-119 (2003)
• [Publications] Harada et al.: "Introduction of wild-type p53 enhances throbospondin-1 expression in human"Cancer Letters. 191. 109-119 (2003)
• [Publications] Gotoh et al.: "The growth inhibitory effect of p21 adenovirus on androgen-dependent and -independent human prostate cancer cells"BJU International. 92. 314-318 (2003)