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

P. Huang, H. Kaku, J. Chen, Y. Kashiwakura, T. Saika, Y. Nasu, Y. Urata, T. Fujiwara, M. Watanabe, H. Kumon

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)484-491
Number of pages8
JournalCancer Gene Therapy
Volume17
Issue number7
DOIs
Publication statusPublished - Jul 2010

Keywords

  • Adenovirus
  • HTERT
  • Interleukin-2
  • OBP-301
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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