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Telomerase-Specific Replication-Selective Virotherapy for Oral Squamous Cell Carcinoma Cell Lines

  • Conference paper
New Trends in the Molecular and Biological Basis for Clinical Oncology

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Abstract

Replication-selective tumor-specific viruses present a novel approach for treating neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. Telomerase activation is considered to be a critical step in carcinogenesis, and its activity is closely correlated with human telomerase reverse transcriptase (hTERT) expression. We investigated the antitumor effect of the hTERT-specific replication-competent adenovirus on oral squamous cell carcinoma (OSCC) cells. An adenovirus 5 vector [tumor- or telomerase-specific replication-competent adenovirus (OBP-301)] was constructed by Center for Gene and Cell Therapy, Okayama University Hospital, in which the hTERT promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site, and we examined the selective replication and antitumor effect in human OSCC cells in vitro and in vivo orthotopic graft model. OBP-301 replicated efficiently and induced more over 50% cell killing in a panel of human OSCC cell lines, but not in normal human fibroblasts, which were lacking telomerase activity. In orthotopic graft model, intratumoral injection of OBP-301 resulted in a significant inhibition of tumor growth and prolongation of survival. Furthermore, mice’s weight recovered as same as before bearing OSCC tumors. Our data clearly indicate that OBP-301 displays an acceptable toxicity profile as well as a therapeutic oncolytic activity for OSCC cells in vitro and in vivo. These results suggested that treatment of OBP-301 is possible to improvement of QOL of oral cancer patients.

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Author information

Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Tokyo, Japan

    Yuji Kurihara, Tatsuo Shirota, Masashi Hatori & Satoru Shintani

  2. Division of Surgical Oncology, Department of Surgery, Okayama University, Graduate School of Medicine and Dentistry, Okayama, Japan

    Tom Kojima & Toshiyoshi Fujiwara

  3. Center for Gene and Cell Therapy, Okayama University Hospital, Okayama, Japan

    Yuichi Watanabe, Tom Kojima & Toshiyoshi Fujiwara

  4. Oncolys BioPharma, Inc., Tokyo, Japan

    Yuichi Watanabe & Yasuo Urata

Authors
  1. Yuji Kurihara
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  2. Yuichi Watanabe
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  3. Tom Kojima
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  4. Tatsuo Shirota
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  5. Masashi Hatori
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  6. Yasuo Urata
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  7. Toshiyoshi Fujiwara
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  8. Satoru Shintani
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Editor information

Editors and Affiliations

  1. Department of Oral Pathology and Diagnosis, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan

    Tetsuhiko Tachikawa D.D.S., Ph.D. (Professor and Chairman) (Professor and Chairman)

  2. Department of Microbiology, Showa University School of Pharmaceutical Sciences, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan

    Kiyoshi Nose Ph.D. (Professor and Chairman) (Professor and Chairman)

  3. Institute of Molecular Oncology, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan

    Tohru Ohmori M.D., Ph.D. (Associate Professor) (Associate Professor)

  4. Division of Allergology and Respiratory Medicine, Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan

    Mitsuru Adachi M.D., Ph.D. (Professor and Chairman) (Professor and Chairman)

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© 2009 Springer

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Kurihara, Y. et al. (2009). Telomerase-Specific Replication-Selective Virotherapy for Oral Squamous Cell Carcinoma Cell Lines. In: Tachikawa, T., Nose, K., Ohmori, T., Adachi, M. (eds) New Trends in the Molecular and Biological Basis for Clinical Oncology. Springer, Tokyo. https://doi.org/10.1007/978-4-431-88663-1_18

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  • DOI: https://doi.org/10.1007/978-4-431-88663-1_18

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-88662-4

  • Online ISBN: 978-4-431-88663-1

  • eBook Packages: MedicineMedicine (R0)

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