A novel antiangiogenic effect for telomerase-specific virotherapy through host immune system

Yoshihiro Ikeda, Toru Kojima, Shinji Kuroda, Yoshikatsu Endo, Ryo Sakai, Masayoshi Hioki, Hiroyuki Kishimoto, Futoshi Uno, Shunsuke Kagawa, Yuichi Watanabe, Yuuri Hashimoto, Yasuo Urata, Noriaki Tanaka, Toshiyoshi Fujiwara

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10 Citations (Scopus)

Abstract

Soluble factors in the tumor microenvironment may influence the process of angiogenesis; a process essential for the growth and progression of malignant tumors. In this study, we describe a novel antiangiogenic effect of conditional replicationselective adenovirus through the stimulation of host immune reaction. An attenuated adenovirus (OBP-301, Telomelysin), in which the human telomerase reverse transcriptase promoter element drives expression of E1 genes, could replicate in and cause selective lysis of cancer cells. Mixed lymphocyte-tumor cell culture demonstrated that OBP-301-infected cancer cells stimulated PBMC to produce IFN-γ into the supernatants. When the supernatants were subjected to the assay of in vitro angiogenesis, the tube formation of HUVECs was inhibited more efficiently than recombinant IFN-γ. Moreover, in vivo angiogenic assay using a membrane-diffusion chamber system s.c. transplanted in nu/nu mice showed that tumor cell-induced neovascularization was markedly reduced when the chambers contained the mixed lymphocyte-tumor cell culture supernatants. The growth of s.c. murine colon tumors in syngenic mice was significantly inhibited due to the reduced vascularity by intratumoral injection of OBP-301. The antitumor as well as antiangiogenic effects, however, were less apparent in SCID mice due to the lack of host immune responses. Our data suggest that OBP-301 seems to have antiangiogenic properties through the stimulation of host immune cells to produce endogenous antiangiogenic factors such as IFN-γ.

Original languageEnglish
Pages (from-to)1763-1769
Number of pages7
JournalJournal of Immunology
Volume182
Issue number3
DOIs
Publication statusPublished - Feb 1 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Ikeda, Y., Kojima, T., Kuroda, S., Endo, Y., Sakai, R., Hioki, M., Kishimoto, H., Uno, F., Kagawa, S., Watanabe, Y., Hashimoto, Y., Urata, Y., Tanaka, N., & Fujiwara, T. (2009). A novel antiangiogenic effect for telomerase-specific virotherapy through host immune system. Journal of Immunology, 182(3), 1763-1769. https://doi.org/10.4049/jimmunol.182.3.1763