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Direct and distant antitumor effects of a telomerase-selective oncolytic adenoviral agent, OBP-301, in a mouse prostate cancer model

Cancer Gene Therapy volume 15, pages 315–322 (2008)Cite this article

Abstract

We previously constructed OBP-301 (Telomelysin, a telomerase-specific replication-competent adenovirus with human telomerase reverse transcriptase (hTERT) promoter), which showed a strong anticancer effect by inducing cell lysis of human non-small cell lung cancer and colorectal cancer cells. To investigate the utility of OBP-301 for prostate cancer treatment, we herein evaluate the cell killing and antitumor effects. First, in vitro hTERT-specific adenovirus transduction in human prostate cancer cells (LNCaP, PC3, DU145) was confirmed using OBP-401 (Telomelysin-green fluorescent protein (GFP)). There was no detectable GFP transduction in the human prostate normal cells (PrEC, PrSC). Consistently, the cell-killing effect of OBP-301 was observed only in the cancer cells. Second, using an in vivo subcutaneous LNCaP tumor model in nude mice, we demonstrated that three intratumoral OBP-301 injections (107 PFU per tumor × 3 days) were sufficient to eradicate the detectable LNCaP prostate tumor. We also demonstrated that the ispilateral treatment with OBP-301 significantly suppressed contralateral LNCaP tumor growth in both sides of the tumor model. Histological and immunohistochemical analyses revealed diffuse oncolytic degeneration and adenoviral E1A protein expression in both sides of the tumors. Therefore, in situ OBP-301 administration could be a promising therapeutic strategy against prostate cancer and its metastatic lesions.

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Acknowledgements

This work was supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology's FY2006 ‘Creation of Innovation Centers for Advanced Interdisciplinary Research Areas’ Scheme in Japan and by a scientific research grant from the Japan Society for the Promotion of Science (C, 18591754; H Kaku). We also thank Yuka Matono, Hideo Ueki and Katsuo Ohno for their valuable technical assistance.

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Authors and Affiliations

  1. Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    P Huang, M Watanabe, H Kaku, J Chen, T Saika, Y Nasu & H Kumon

  2. Innovation Center Okayama for Nanobio-Targeted Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    M Watanabe, Y Kashiwakura & H Kumon

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

    H Kaku, T Fujiwara & H Kumon

  4. Oncolys BioPharma Inc., Tokyo, Japan

    Y Urata

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  1. P Huang
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Correspondence to Y Nasu.

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Huang, P., Watanabe, M., Kaku, H. et al. Direct and distant antitumor effects of a telomerase-selective oncolytic adenoviral agent, OBP-301, in a mouse prostate cancer model. Cancer Gene Ther 15, 315–322 (2008). https://doi.org/10.1038/cgt.2008.3

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