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Potent antitumor effects of combined therapy with a telomerase-specific, replication-competent adenovirus (OBP-301) and IL-2 in a mouse model of renal cell carcinoma

Cancer Gene Therapy volume 17, pages 484–491 (2010)Cite this article

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Abstract

OBP-301 (a telomerase-specific, replication-competent adenovirus with hTERT promoter) was constructed in a previous study and it showed a strong anticancer effect by inducing cell lysis in human lung and prostate cancer cells. This study investigated the effectiveness of a combination therapy of OBP-301 and interleukin-2 (IL-2) in a mouse model of renal cell carcinoma (RCC). The cell-killing effect of OBP-301 was confirmed in vitro in the RENCA cancer cells. In in vivo experiment, luciferase-expressing RENCA cells were implanted in the left kidney and lung of BALB/c mice to prepare the RCC metastatic model. The animals were randomly divided into four treatment groups: PBS, IL-2 alone, OBP-301 alone and the combination. The analyses of orthotopic tumor weight, lung metastasis and luciferin-stained tumor images 14 days after each treatment showed significant tumor growth inhibition in the combination group in comparison with that in the OBP-301- or IL-2-treated groups. In addition, the percentage of regulatory T-cells (Tregs) in the combination group was significantly suppressed in comparison with that in the PBS and single-agent treatment groups. The outcomes of this study suggest that tumor-specific oncolytic immunovirotherapy may become an attractive strategy for the treatment of human RCC.

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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. We also thank Hideo Ueki and Katsuo Ohno for 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, H Kaku, J Chen, T Saika, Y Nasu, M Watanabe & H Kumon

  2. Center for Gene and Cell Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    H Kaku, T Fujiwara & H Kumon

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

    Y Kashiwakura, M Watanabe & H Kumon

  4. Oncolys BioPharma Inc., Tokyo, Japan

    Y Urata

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  1. P Huang
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Correspondence to P Huang.

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Huang, P., Kaku, H., Chen, J. et al. Potent antitumor effects of combined therapy with a telomerase-specific, replication-competent adenovirus (OBP-301) and IL-2 in a mouse model of renal cell carcinoma. Cancer Gene Ther 17, 484–491 (2010). https://doi.org/10.1038/cgt.2010.5

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