title: Whole cell vaccination using immunogenic cell death by an oncolytic adenovirus is effective against a colorectal cancer model.
abstract: Cancer vaccine application is limited to specific cancer types because few cancer-associated antigens are known to induce tumor rejection. Accordingly, we assessed the utility of Ad881, an oncolytic adenovirus in which viral replication was strictly regulated by the cancer-specific midkine promoter, as a cancer vaccine in a murine colorectal cancer model lacking specific cancer-associated antigens. In CT26 and CMT93 cells, Ad881 (multiplicity of infection: 100 or 1,000) showed stronger cytotoxicity and oncolysisin vitrothan its equivalent replication-defective adenovirus, Ad884. CT26 cells (1 × 104) infected with Ad881 (multiplicity of infection: 1,000) for 24 hours were suitable as vaccine antigens without tumor formation in our model. Repeated vaccinations, but not single vaccination, induced a greater prophylactic immune response. The percentage of mice that rejected the tumor challenge was 0, 4, and 38% after no vaccination, single vaccination, and repeated vaccinations, respectively. Immunogenic cell death marker high-mobility group box 1 protein (HMGB1) and adenosine triphosphate in culture medium were higher after Ad881 infection (24.3 ng/ml and 48.2 nmol/l, respectively) than after Ad884 infection (8.6 ng/ml and 15.4 nmol/l, respectively) or oxaliplatin treatment (3.7 ng/ml and 1.8 nmol/l, respectively). These results indicate that repeated whole cell vaccination using an oncolytic adenovirus may be a potent approach to evoke immunogenic cell death.
authors.affiliation: Division of Lower Gastrointestinal Surgery, Department of Surgery , Hyogo College of Medicine , Nishinomiya, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Yamano
authors.affiliation: Department of Genetics , Hyogo College of Medicine , Nishinomiya, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Kubo
authors.affiliation: Division of Lower Gastrointestinal Surgery, Department of Surgery , Hyogo College of Medicine , Nishinomiya, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Fukumoto
authors.affiliation: Division of Lower Gastrointestinal Surgery, Department of Surgery , Hyogo College of Medicine , Nishinomiya, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Yano
authors.affiliation: Department of Genetics , Hyogo College of Medicine , Nishinomiya, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Mawatari-Furukawa
authors.affiliation: Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine , Nishinomiya, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Okamura
authors.affiliation: Division of Lower Gastrointestinal Surgery, Department of Surgery , Hyogo College of Medicine , Nishinomiya, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Tomita