title: Oncolytic herpes virus induces effective anti-cancer immunity against murine colon cancer.
abstract: BACK GROUND/AIMS: Oncolytic virus therapy is becoming a promising anti-cancer therapy and oncolytic viruses have been shown to elicit anti-cancer immunity. We evaluated the anti-tumor immune responses elicited by the herpes oncolytic virus R3616 compared to a representative chemotherapy drug, 5-FU.
  
  
  METHODS
  R3616 or 5-FU was directly injected into subcutaneous tumors of non-immunized mice. Additionally, complete adjuvant, R3616-infected MC26 cells or 5-FU plus MC26 cells were frozen, thawed and used to immunize mice. After 21 days of immunization, the adaptive immune response suppressed implanted tumor growth and prolonged survival rate. We monitored differences in the number of infiltrating CD8- and CD4-positive lymphocytes in implanted tumors by immunofluorescence.
  
  
  RESULTS
  R3616 induced a statistically greater number of infiltrating T cells (Thy1.2), macrophages (CD68) and dendritic cells (CD83) in injected tumors than 5-FU. The group immunized with R3616-infected MC26 cells had greater tumor suppression and longer survival rate than non-immunized mice and mice treated with 5-FU plus MC26 cells with statistically significant differences between these groups. The mice immunized with R3616-infected MC26 cells had a statistically greater number of infiltrating T cells in the implanted tumor than non-immunized and mice treated with 5-FU plus MC26 cells.
  
  
  CONCLUSIONS
  These results indicate that oncolytic herpes virus R3616 can elicit more effective host anti-tumor immune responses than 5-FU against murine colon cancer model.
authors.affiliation: Department of Surgery II, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shirota
authors.forename: Hideki
authors.initials: H
authors.lastname: Kasuya
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nishikawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Shikano
authors.forename: Tevfik Tolga
authors.initials: TT
authors.lastname: Sahin
authors.forename: Tan
authors.initials: T
authors.lastname: Gewen
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamamura
authors.forename: Saori
authors.initials: S
authors.lastname: Fukuda
authors.forename: Akiyuki
authors.initials: A
authors.lastname: Kanzaki
authors.forename: Suguru
authors.initials: S
authors.lastname: Yamada
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujii
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Shuji
authors.initials: S
authors.lastname: Nomoto
authors.forename: Shin
authors.initials: S
authors.lastname: Takeda
authors.forename: Akimasa
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000276:immunology* / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D006564:Herpesviridae / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000276:immunology*; D014407:Tumor Cells, Cultured