Intravenous injection of irradiated tumor cell vaccine carrying oncolytic adenovirus suppressed the growth of multiple lung tumors in a mouse squamous cell carcinoma model

Aya Saito, Naoya Morishita, Chihomi Mitsuoka, Shunichi Kitajima, Katsuyuki Hamada, Kyung-Mi Lee, Masato Kawabata, Masato Fujisawa, Toshiro Shirakawa

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Although cancer therapy using replication-selective oncolytic adenoviruses has been available for many years, its anti-tumor efficacy is suboptimal as a result of low and nonspecific infectivity that depends on coxsackie adenovirus receptor expression of the target cancer and normal cells, and generation of an anti-adenovirus neutralizing antibody. In addition, concerns of triggering a severe innate immune response against the adenovirus limit the systemic administration. We developed the carrier cell-based oncolytic virus system (CBOVS) using irradiated tumor cells as carrier cells and concealing the adenovirus (Ad-IAI.3B) inside to improve the specific infectivity. We investigated the anti-tumor effect of CBOVS in a multiple lung tumor mouse model. Methods: The ability of CBOVS to infect Ad-IAI.3B to the target cancer cells was examined in vitro in the presence of anti-adenovirus antibodies. To evaluate the systemic effect of CBOVS, we intravenously injected CBOVS into mice with lung tumors (KLN205 cell lines). Results: CBOVS enhanced the infectivity of Ad-IAI.3B to tumor cells in the presence of anti-adenovirus antibodies in vitro. Intravenous injections of CBOVS produced an accumulation of the adenovirus in the lung-bearing tumors and produced a strong anti-tumor effect in vivo. Furthermore, lymphocytes collected from the CBOVS-treated mice induced an increase in cytokines related to the Th1 response (interferon-γ, interleukin-12) by pulsing with KLN205. Conclusions: These findings suggest that CBOVS could protect adenoviruses from neutralizing antibodies and systemically deliver them to lung tumors. Furthermore, CBOVS appears to have potential as a tumor cell vaccine that activates cytotoxic immunity against cancer cells.

Original languageEnglish
Pages (from-to)353-361
Number of pages9
JournalJournal of Gene Medicine
Volume13
Issue number6
DOIs
Publication statusPublished - 2011 Jun 1

Keywords

  • Adenovirus
  • Carrier cell
  • Gene therapy
  • Immune therapy
  • Squamous cell carcinoma
  • Tumor cell vaccine

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)
  • Drug Discovery

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