title: Intravenous injection of irradiated tumor cell vaccine carrying oncolytic adenovirus suppressed the growth of multiple lung tumors in a mouse squamous cell carcinoma model.
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.
authors.affiliation: Division of Infectious Disease Control, Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Saito
authors.forename: Naoya
authors.initials: N
authors.lastname: Morishita
authors.forename: Chihomi
authors.initials: C
authors.lastname: Mitsuoka
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kitajima
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hamada
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Lee
authors.forename: Masato
authors.initials: M
authors.lastname: Kawabata
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Shirakawa
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000517:prevention & control*; D018929:Cell Culture Techniques; D016207:Cytokines / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D050504:Oncolytic Viruses / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D017931:DNA Primers