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

초록

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-gamma, 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. Copyright (C) 2011 John Wiley & Sons, Ltd.

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