title: In situ cancer vaccination with a replication-conditional HSV for the treatment of liver metastasis of colon cancer.
abstract: In this study, we investigated the therapeutic efficacy of a replication-conditional mutant HSV, G207, for the treatment of liver metastasis of colon carcinoma. Three liver metastasis models in syngeneic BALB/c mice were developed: (i) splenic injection, (ii) splenic and subcutaneous (s.c.) injection, and (iii) orthotopic implantation of CT26 colon carcinoma. In the splenic injection model, G207 was injected into the established splenic tumor on day 7. In the splenic and s.c. injection model, G207 were injected into the established s.c. tumor on days 5 and 8. In the orthotopic implantation model, a piece of CT26 tumor tissue was transplanted onto the wall of the cecum and G207 was injected in the established cecum tumor on day 7. On day 21 or 28, animals were sacrificed and liver metastases were evaluated. In all three models in immunocompetent mice, liver metastases were significantly reduced by intratumoral inoculation with G207 compared to the control. In athymic mice, however, there was no significant therapeutic effect of intratumoral inoculation with G207 on liver metastases. Tumor-specific cytotoxic T-lymphocyte responses were induced in mice treated with G207 in the orthotopic implantation model. These results suggest that intratumoral inoculation of G207, as an in situ cancer vaccine, can be an effective approach against liver metastasis of colon cancer and the efficacy involves tumor-specific T-cell responses.
authors.affiliation: Department of Surgery, Institute for Advanced Medical Research, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Endo
authors.forename: Masahiro
authors.initials: M
authors.lastname: Toda
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Iizuka
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kubota
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitajima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D015552:Injections, Intralesional; D008113:Liver Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D018139:Simplexvirus / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D014779:Virus Replication / Q000235:genetics*
chemical_list: D019496:Cancer Vaccines