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

摘要

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.