Molecular therapy for gastric cancer using HER2-extracellular domain-expressing adenovirus

• Project/Area Number: 22390256
• 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, 大学院・医歯薬学総合研究科, 教授 (00304303)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2011: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2010: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
• Keywords: HER2 / ADCC / 乳癌 / 胃癌 / アデノウイルス / 分子標的医薬品 / 抗体医薬品 / トラスツズマブtrasutuzumab / トラスツズマブ

Research Abstract

Trastuzumab, a humanized antibody targeting HER2, exhibits remarkable therapeutic efficacy against HER2-positive breast and gastric cancers. We found that exogenous HER2-extracellular domain (ECD) expression had no apparent effect on the signaling pathway, but strongly enhanced antibody-dependent cellular cytotoxicity (ADCC) activity in low HER2-expressing or trastuzumab-resistant human cancer cells.

Research Products

• [Journal Article] The hTERT promoter enhances the antitumor activity of an oncolytic adenovirus under a hypoxic microenvironment (2013)
  • Author(s): Hashimoto, Y., Tazawa, H., Teraishi, F., Kojima, T., Watanabe, Y., Uno, F., Yano, S., Urata, Y., Kagawa, S., Fujiwara, T.
  • Journal Title: PLoS One Volume: (inpress)
  • NAID: 120005232484
  • Peer Reviewed
• [Journal Article] Multicenter phase II study of S-1 and docetaxel combination chemotherapy for advanced or recurrent gastric cancer patients with peritoneal dissemination (2013)
  • Author(s): Shigeyasu, K., Kagawa, S., Uno, F., Nishizaki, M., Kishimoto, H., Gochi, A., Kimura, T., Takahata, T., Nonaka, Y., Ninomiya, M., Fujiwara, T.
  • Journal Title: Cancer Chemother. Pharmacol Volume: 71 Pages: 937-943
  • Peer Reviewed
• [Journal Article] A novel synergistic effect of iron depletion on anti-angiogenic cancer therapy (2013)
  • Author(s): Ohara, T., Noma, K., Urano, S., Watanabe, S., Nishitani, S., Tomono, Y., Kimura, F., Kagawa, S., Shirakawa, Y., Fujiwara, T.
  • Journal Title: Int. J. Cancer Volume: 132 Pages: 2705-2713
  • Peer Reviewed
• [Journal Article] Dual programmed cell death pathways induced by p53 transactivation overcome resistance to oncolytic adenovirus in human osteosarcoma cells. (2013)
  • Author(s): Hasei, J., Sasaki, T., Tazawa, H., Osaki, S., Yamakawa, Y., Kunisada, T., Yoshida, A., Hashimoto, Y., Onishi, T., Uno, F., Kagawa, S., Urata, Y., Ozaki, T., Fujiwara, T.
  • Journal Title: Dual programmed cell death pathways induced by p53 transactivation overcome resistance to oncolytic adenovirus in human osteosarcoma cells. Volume: 12 Pages: 314-325
  • NAID: 120005324798
  • Peer Reviewed
• [Journal Article] A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus. (2013)
  • Author(s): Sasaki, T., Tazawa, H., Hasei, J., Osaki, S., Kunisada, T., Yoshida, A., Hashimoto, Y., Yano, S., Yoshida, R., Kagawa, S., Uno, F., Urata, Y., Ozaki, T., Fujiwara, T
  • Journal Title: Gene Ther. Volume: 20 Pages: 112-118
  • Peer Reviewed
• [Journal Article] Dual programmed cell death pathways induced by p53 transactivation overcome resistance to oncolytic adenovirus in human osteosarcoma cells. (2013)
  • Author(s): Hasei, J.
  • Journal Title: Molecular Cancer Therapeutics Volume: 12 Issue: 3 Pages: 314-325
  • DOI: 10.1158/1535-7163.mct-12-0869
  • Peer Reviewed
• [Journal Article] A novel apoptotic mechanism of genetically engineered adenovirus-mediated tumour-specific p53 overexpression through E1A-dependent p21 and MDM2 suppression. (2012)
  • Author(s): Yamasaki, Y., Tazawa, H., Hashimoto, Y., Kojima, T., Kuroda, S., Yano, S., Yoshida, R., Uno, F., Mizuguchi, H., Ohtsuru, A., Urata, Y., Kagawa, S., Fujiwara, T.
  • Journal Title: Eur. J. Cancer Volume: 48 Pages: 2282-2291
  • Peer Reviewed
• [Journal Article] Genetically engineered oncolytic adenovirus induces autophagic cell death through an E2F1-microRNA-7-epidermal growth factor receptor axis. (2012)
  • Author(s): Tazawa, H., Yano, S., Yoshida, R., Yamasaki, Y., Sasaki, T., Hashimoto, Y., Kuroda, S., Ouchi, M., Onishi, T., Uno, F., Kagawa, S., Urata, Y., Fujiwara, T.
  • Journal Title: Int. J. Cancer Volume: 131 Pages: 2939-2950
  • NAID: 130004505785
  • Peer Reviewed
• [Journal Article] Mechanism of resistance to trastuzumab and molecular sensitization via ADCC activation by exogenous expression of HER2-extracellular domain in human cancer cells. (2012)
  • Author(s): Yoshida, R., Tazawa, H., Hashimoto, Y., Yano, S., Onishi, T., Sasaki, T., Shirakawa, Y., Kishimoto, H., Uno, F., Nishizaki, M., Kagawa, S., Fujiwara, T
  • Journal Title: Cancer Immuno. Immunother. Volume: 61 Pages: 1905-1916
  • NAID: 120005232490
  • Peer Reviewed
• [Journal Article] Enhanced antitumor efficacy of telomerase-specific oncolytic adenovirus with valproic acid against human cancer cells. (2012)
  • Author(s): Watanabe, Y., Hashimoto, Y., Kagawa, S., Kawamura, H., Nagai, K., Tanaka, N., Urata, Y., Fujiwara, T.
  • Journal Title: Cancer Gene Ther. Volume: 19 Pages: 767-772
  • Peer Reviewed
• [Journal Article] Mechanism of resistance to trastuzumab and molecular sensitization via ADCC activation by exogenous expression of HER2-extracellular domain in human cancer cells. (2012)
  • Author(s): Yoshida, R.
  • Journal Title: Cancer Immunology, Immunotherapy Volume: 61 Issue: 11 Pages: 1905-1916
  • DOI: 10.1007/s00262-012-1249-x
  • Peer Reviewed
• [Journal Article] A novel apoptotic mechanism of genetically engineered adenovirus-mediated tumour-specific p53 overexpression through E1A-dependent p21 and MDM2 suppression (2012)
  • Author(s): Yamasaki, Y.
  • Journal Title: European Journal of Cancer Volume: (Epub ahead of print) Issue: 14 Pages: 2282-2291
  • DOI: 10.1016/j.ejca.2011.12.020
  • Peer Reviewed
• [Journal Article] Genetically engineered oncolytic adenovirus induces autophagic cell death through an E2F1-microRNA-7-epidermal growth factor receptor axis (2012)
  • Author(s): Tazawa, H.
  • Journal Title: International Journal of Cancer Volume: (Epub ahead of print) Issue: 12 Pages: 2939-2950
  • DOI: 10.1002/ijc.27589
  • Peer Reviewed
• [Journal Article] Enhanced antitumor efficacy of telomerase-specific oncolytic adenovirus with valproic acid against human cancer cells. (2012)
  • Author(s): Watanabe, Y.
  • Journal Title: Cancer Gene Therapy Volume: 19 Issue: 11 Pages: 767-772
  • DOI: 10.1038/cgt.2012.57
  • Peer Reviewed
• [Journal Article] A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus (2012)
  • Author(s): Sasaki, T.
  • Journal Title: Gene Therapy Volume: (Epub ahead of print) Issue: 1 Pages: 112-118
  • DOI: 10.1038/gt.2011.213
  • Peer Reviewed
• [Journal Article] Preclinical evaluation of telomerase-specific oncolytic virotherapy for human bone and soft tissue sarcomas. (2011)
  • Author(s): Sasaki, T., Tazawa, H., Hasei, J., Kunisada, T., Yoshida, A., Hashimoto, Y., Yano, S., Yoshida, R., Uno, F., Kagawa, S., Morimoto, Y., Urata, Y., Ozaki, T., Fujiwara, T.
  • Journal Title: Clin. Cancer Res. Volume: 17 Pages: 1828-1838
  • NAID: 130004505755
  • Peer Reviewed
• [Journal Article] Enhanced safety profiles of the telomerase-specific replication-competent adenovirus by incorporation of normal cell-specific microRNA-targeted sequences (2011)
  • Author(s): Sugio, K., Sakurai, F., Katayama, K., Tashiro, K., Matsui, H., Kawabata, K., Kawase, A., Iwaki, M., Hayakawa, T., Fujiwara, T., Mizuguchi, H.
  • Journal Title: Clin. Cancer Res. Volume: 17 Pages: 2807-2818
  • Peer Reviewed
• [Journal Article] Inhibition of mTOR by temsirolimus contributes to prolonged survival of mice with pleural dissemination of non-small-cell lung cancer cells (2011)
  • Author(s): Ohara, T., Takaoka, M., Toyooka, S., Tomono, Y., Nishikawa, T., Shirakawa, Y., Yamatsuji, T., Tanaka, N., Fujiwara, T., Naomoto, Y.
  • Journal Title: Cancer Sci. Volume: 102 Pages: 1344-1349
  • NAID: 10029295354
  • Peer Reviewed
• [Journal Article] Tumor-selective, adenoviral-mediated GFP genetic labeling of human cancer in the live mouse reports future recurrence after resection. (2011)
  • Author(s): Kishimoto, H., Aki, R., Urata, Y., Bouvet, M., Momiyama, M., Tanaka, N., Fujiwara, T., Hoffman, R. M.
  • Journal Title: Cell Cycle Volume: 10 Pages: 2737-2741
  • Peer Reviewed
• [Journal Article] MicroRNAs as potential target gene in cancer gene therapy of gastrointestinal tumors (2011)
  • Author(s): Tazawa H, et al
  • Journal Title: Expert Opinion on Biological Therapy Volume: 11 Issue: 2 Pages: 145-155
  • DOI: 10.1517/14712598.2011.542749
  • Peer Reviewed
• [Journal Article] Preclinical evaluation of telomerase-specific oncolytic virotherapy for human bone and soft tissue sarcomas (2011)
  • Author(s): Sasaki T, et al
  • Journal Title: Clinical Cancer Research Volume: 17 Issue: 7 Pages: 1828-1838
  • DOI: 10.1158/1078-0432.ccr-10-2066
  • Peer Reviewed
• [Journal Article] Telomerase-specific oncolytic virotherapy Tor human gastrointestinal cancer (2011)
  • Author(s): Fujiwara T, et al
  • Journal Title: Expert Review of Anticancer Therapy Volume: 11 Issue: 4 Pages: 525-532
  • DOI: 10.1586/era.10.200
  • Peer Reviewed
• [Journal Article] A phase I study of telomerase-specific replication competent oncolytic adenovirus (telomelysin) for various solid tumors. (2010)
  • Author(s): Nemunaitis, J., Tong, A. W., Nemunaitis, M., Senzer, N., Phadke, A. P., Bedell, C., Adams, N., Zhang, Y. A., Maple, P. B., Chen, S., Pappen, B., Burke, J., Ichimaru, D., Urata, Y., Fujiwara, T.
  • Journal Title: Mol. Ther. Volume: 18 Pages: 429-34
  • Peer Reviewed
• [Journal Article] A novel translational approach for human malignant pleural mesothelioma: heparanase-assisted dual virotherapy. (2010)
  • Author(s): Watanabe, Y., Kojima, T., Kagawa, S., Uno, F., Hashimoto, Y., Kyo, S., Mizuguchi, H., Tanaka, N., Kawamura, H., Ichimaru, D., Urata, Y., Fujiwara, T.
  • Journal Title: Oncogene Volume: 29 Pages: 1145-1154
  • Peer Reviewed
• [Journal Article] n vivo biological purging for lymph node metastasis of human colorectal cancer by telomerase-specific oncolytic virotherapy. (2010)
  • Author(s): Kojima, T., Watanabe, Y., Hashimoto, Y., Kuroda, S., Yamasaki, Y., Yano, S., Ouchi, M., Tazawa, H., Uno, F., Kagawa, S., Kyo, S., Mizuguchi, H., Urata, Y., Tanaka, N., Fujiwara, T.
  • Journal Title: Ann. Surg. Volume: 251 Pages: 1079-1086
  • Peer Reviewed
• [Journal Article] Preclinical evaluation of differentially targeting dual virotherapy for human solid cancer. (2010)
  • Author(s): Sakai, R., Kagawa, S., Yamasaki, Y., Kojima, T., Uno, F., Hashimoto, Y., Watanabe, Y., Urata, Y., Tanaka, N., Fujiwara, T
  • Journal Title: Mol. Cancer Ther. Volume: 9 Pages: 1884-1893
  • Peer Reviewed
• [Journal Article] Telomerase-dependent oncolytic adenovirus sensitizes human cancer cells to ionizing radiation via inhibition of DNA repair machinery (2010)
  • Author(s): Kuroda, S., Fujiwara, T., Shirakawa, Y., Yamasaki, Y., Yano, S., Uno, F., Tazawa, H., Hashimoto, Y., Watanabe, Y., Noma, K., Urata, Y., Kagawa, S., Fujiwara, T.
  • Journal Title: Cancer Res. Volume: 70 Pages: 9339-9348
  • Peer Reviewed
• [Journal Article] In vivo biological purging for lymph node metastasis of human colorectal cancer by telomerase-specific oncolytic virotherapy. (2010)
  • Author(s): Kojima, T.
  • Journal Title: Annals of Surgery Volume: 251 Pages: 1079-1086
  • Peer Reviewed
• [Journal Article] Preclinical evaluation of differentially targeting dual virotherapy for human solid cancer. (2010)
  • Author(s): Sakai, R.
  • Journal Title: Molecular Cancer Terapeutics Volume: 9 Pages: 1884-1893
  • Peer Reviewed
• [Journal Article] Telomerase-dependent oncolytic adenovirus sensitizes human cancer cells to ionizing radiation via inhibition of DNA repair machinery. (2010)
  • Author(s): Kuroda, S.
  • Journal Title: Cancer Research Volume: 70 Pages: 9339-9348
  • Peer Reviewed
• [Presentation] 消化器がん治療における遺伝子工学技術に基づく先端医療開発 (2012)
  • Author(s): 藤原俊義
  • Organizer: 第20回日本消化器関連学会週間(第10回日本消化器外科学会大会)
  • Place of Presentation: 神戸
  • Year and Date: 2012-10-12
• [Presentation] 消化器がん治療における遺伝子工学技術に基づく先端医療開発. (2012)
  • Author(s): 藤原俊義
  • Organizer: 第10回日本消化器外科学会大会
  • Place of Presentation: 神戸
  • Invited
• [Presentation] アカデミアにおける探索的医薬品開発の方向性～国産ウイルス製剤の米国での臨床試験への道程～ (2011)
  • Author(s): 藤原俊義
  • Organizer: 第11回CRCと臨床試験のあり方を考える会議(特別講演[)
  • Place of Presentation: 岡山
  • Year and Date: 2011-09-24
• [Presentation] Molecular imaging and multidisciplinary therapy for human cancer with elomerase-specific oncolytic adenovirus (2011)
  • Author(s): Fujiwara, T
  • Organizer: 8th International Symposium on Minimal Residual Cancer (Plenary Lecture)
  • Place of Presentation: Osaka
  • Year and Date: 2011-09-22
• [Presentation] Telomerase-specific oncolytic virotherapy for human cancer. (2011)
  • Author(s): Fujiwara, T.
  • Organizer: US-Japan Joint Seminars "Trend of gene& cell therapy as translational research in USA and Japan"
  • Place of Presentation: Fukuoka
  • Year and Date: 2011-07-14
• [Presentation] Molecular imaging and multidisciplinary therapy for human cancer with telomerase-specific replication-selective adenovirus. (2011)
  • Author(s): Fujiwara, T., Urata, Y.
  • Organizer: 第17回日本遺伝子治療学会(シンポジウム)
  • Place of Presentation: 福岡
  • Year and Date: 2011-07-06
• [Presentation] テロメラーゼ活性を標的とするウイルス製剤の癌診断・治療への応用. (2011)
  • Author(s): 藤原俊義、浦田泰生
  • Organizer: 第20回癌病態治療研究会(シンポジウム)
  • Place of Presentation: 東京
  • Year and Date: 2011-06-17
• [Presentation] Telomerase-specific oncolytic adenovirus for human cancer therapy and diagnostic imaging. (2011)
  • Author(s): Fujiwara, T.
  • Organizer: 14th Annual Meeting of American Society of Gene & Cell Therapy: Scientific Symposium "Viral Vecors for Immunomodulation of Cancer: From Bench to Bed"
  • Place of Presentation: Seattle(USA)
  • Year and Date: 2011-05-20
• [Presentation] Telomerase-specific oncolytic adenovirus for human cancer therapy and diagnostic imaging (2011)
  • Author(s): Fujiwara T
  • Organizer: 14th Annual Meeting of American Society of Gene & Cell Therapy
  • Place of Presentation: Seattle, USA
  • Year and Date: 2011-05-20
• [Presentation] Detection of viable human circulating tumor cells using telomerase-specific GFP-expressing bioengineered adenovirus in patients with gastric cancer: A fiesibility study. (2011)
  • Author(s): Fujiwara, T., Uno, F., Hashimoto, Y., Shirakawa, Y., Nagasaka, T., Kagawa, S., Urata, Y.
  • Organizer: 2011 ASCO Gastrointestinal Cancer Symposium
  • Place of Presentation: San Francisco(USA)
  • Year and Date: 2011-01-20
• [Presentation] Theranostic application of telomerase-specific replication-selective adenosurs for human cancer. (2010)
  • Author(s): 藤原俊義
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] Molecular imging of human cancer with telomerase-specific replication-selective adenovirus. (2010)
  • Author(s): Fujiwara, T.
  • Organizer: Pre-conference Satellite Meeting of World Molecular Imaging Conference "Shedding Light for Unveiling Life"
  • Place of Presentation: Seoul(Korea)
  • Year and Date: 2010-09-06
• [Presentation] 遺伝子改変ウイルス製剤を用いた蛍光イメージングによる血中循環がん細胞(CTC)の検出 (2010)
  • Author(s): 藤原俊義、宇野太、田澤大、香川俊輔、児島亨、矢野修也、吉田亮介、橋本悠里、浦田泰生
  • Organizer: 第65回日本消化器外科学会総会
  • Place of Presentation: 山口
  • Year and Date: 2010-07-16
• [Presentation] Phase I clinical trial of telomerase-specific oncolytic adenovirus for advanced solid tumors. (2010)
  • Author(s): Fujiwara, T., Urata, Y., Nemunaitis, J
  • Organizer: 第16回日本遺伝子治療学会
  • Place of Presentation: 宇都宮
  • Year and Date: 2010-07-02
• [Presentation] Telomerase-specific molecular radiosensitizer for human cancer (2010)
  • Author(s): 藤原俊義
  • Organizer: 第49回日本生体医工学会大会
  • Place of Presentation: 大阪
  • Year and Date: 2010-06-27
• [Presentation] テロメラーゼ活性を標的とするウイルス製剤の癌診断・治療への応用. (2010)
  • Author(s): 藤原俊義
  • Organizer: 第110回日本外科学会定期学術集会(ワークショップ)
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-08
• [Book] In vivo imaging of human cancer with telomerase-specific replication-selective adenovirus. In "In Vivo Vellular Imaging Using Fluorescent Proteins" (Hoffman, R. B., ed.) (2012)
  • Author(s): Fujiwara, T
  • Publisher: Humana Press, c/o Springer Science + Business Media, LLC, New York, USA