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 | Zendy

Peng Huang | Zendy; Haruki Kaku | Zendy; J Chen | Zendy; Yuji Kashiwakura | Zendy; Takashi Saika | Zendy; Yasutomo Nasu | Zendy; Y. Urata | Zendy; Toshiyoshi Fujiwara | Zendy; Masami Watanabe | Zendy; Hiromi Kumon | Zendy

Open Access

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

Author(s) -

Peng Huang,

Haruki Kaku,

J Chen,

Yuji Kashiwakura,

Takashi Saika,

Yasutomo Nasu,

Y. Urata,

Toshiyoshi Fujiwara,

Masami Watanabe,

Hiromi Kumon

Publication year - 2010

Publication title -

cancer gene therapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.535

H-Index - 86

eISSN - 1476-5500

pISSN - 0929-1903

DOI - 10.1038/cgt.2010.5

Subject(s) - telomerase , oncolytic virus , telomerase reverse transcriptase , oncolytic adenovirus , in vivo , cancer research , virotherapy , renal cell carcinoma , combination therapy , medicine , prostate cancer , cancer , immunology , biology , pharmacology , tumor cells , biochemistry , microbiology and biotechnology , gene

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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