title: Enhancement of systemic tumor immunity for squamous cell carcinoma cells by an oncolytic herpes simplex virus.
abstract: RH2 is a neurovirulent γ134.5 gene-deficient herpes simplex virus type 1 (HSV-1) with a lytic ability in human squamous cell carcinoma (SCC) cells; it is related to spontaneously occurring HSV-1 mutant HF10. The effect of RH2 on SCC was examined using a syngeneic C3H mouse model. After infection of mouse SCCVII cells with RH2, cell viability was decreased at first, but recovered by prolonged culture, indicating the limited replication of RH2. The antitumor ability of RH2 was examined using a bilateral SCCVII tumor model. The growth of the RH2-injected tumors was suppressed compared with that of phosphate-buffered saline-injected tumors. Moreover, the growth of contralateral tumor of RH2-treated mice was also suppressed significantly. The splenocytes of C3H mice treated with RH2 lysed more SCCVII cells than NFSaY83 cells and YAC-1 cells. The cytotoxicity of the splenocytes on SCCVII cells was significantly greater than that of splenocytes from tumor-bearing mice. Removal of CD8(+) T cells from splenocytes decreased their cell killing activity remarkably. The antitumor effect of RH2 on SCCVII xenografts in nude mice was not demonstrated. These results indicate that RH2 exhibited a suppressive effect on mouse SCC, even if the replication of RH2 was limited. This is ascribed to the ability of RH2 to enhance existing tumor-specific cytotoxic T lymphocyte activity.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Meshii
authors.forename: G
authors.initials: G
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Okunaga
authors.forename: M
authors.initials: M
authors.lastname: Hamada
authors.forename: S
authors.initials: S
authors.lastname: Iwai
authors.forename: A
authors.initials: A
authors.lastname: Takasu
authors.forename: Y
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Y
authors.initials: Y
authors.lastname: Yura
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D050504:Oncolytic Viruses / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014161:Transduction, Genetic; D019076:Transgenes; D047368:Tumor Burden / Q000235:genetics