Telomerase-Specific Oncolytic Virotherapy for Human Cancer with the hTERT Promoter

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  • FUJIWARA Toshiyoshi
    Center for Gene and Cell Therapy, Okayama University Hospital Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
  • TANAKA Noriaki
    Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

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  • テロメラーゼ活性を標的とした悪性腫瘍に対するウイルス療法の開発
  • テロメラーゼ カッセイ オ ヒョウテキ ト シタ アクセイ シュヨウ ニ タイスル ウイルス リョウホウ ノ カイハツ

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Abstract

Replication-selective tumor-specific viruses present a novel approach for treatment of neoplastic disease. Telomerase activation is considered to be a critical step in carcinogenesis and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. We constructed an attenuated adenovirus 5 vector (Telomelysin, OBP-301), in which the hTERT promoter element drives expression of E1 genes. Telomelysin replicated efficiently and induced marked cell killing in a panel of human cancer cell lines, whereas replication as well as cytotoxicity was highly attenuated in normal human cells lacking telomerase activity. We further modified the E3 region of OBP-301 to contain green fluorescent protein (GFP) gene for monitoring viral replication (TelomeScan, OBP-401). When TelomeScan was intratumorally injected into human tumors orthotopically implanted into the rectum in mice, para-aortic lymph node metastasis could be visualized at laparotomy under a three-chip color cooled charged-coupled device camera. This article reviews recent highlights in this rapidly evolving field: cancer therapeutic and cancer diagnostic approaches using the telomerase-specific oncolytic adenoviruses.

Journal

  • Uirusu

    Uirusu 58 (1), 11-18, 2008

    The Japanese Society for Virology

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