Immune analysis on mtHSV mediated tumor therapy in HSV-1 seropositive mice

We previously reported that the mutant virus of HSV (mtHSV) mediated tumor therapy was efficacious in Balb/c and nude mice. However, it is significant to know whether mtHSV works in HSV-1 tumor seropositive individuals because many patients with HSV-1 seropositivity have been found in clinical trial. Here we asked whether the oncolytic effect of mtHSV is influenced under condition of HSV-1 seropositivity. In this study, Balb/c mice were immunized intraperitoneally with mtHSV and HSV-1 F. Subsequently, HSV seropositive and naive Balb/c mice were inoculated with sarcoma 180 cells in the armpit of left forelimb and then were treated with mtHSV intratumorally. The results shown that the growth of tumor in HSV-1 F seropositive mice was inhibited dramatically after treatment with mtHSV; and significant differences in mean tumor growth ratio were found compared with the groups of mtHSV seropositive mice and naive mice. These data demonstrated that the effect of mtHSV-mediated tumor therapy couldn’t be weaken but enhanced by HSV seropositivity. Furthermore, comparison of in vitro cytotoxicity to S-180 cells of PBMC from HSV seropositive and naive mice showed PBMC from HSV-1 F seropositive had the highest killing percentage. Cytokines transcription level of PBMC showed IFN-g were enhanced remarkably in early and late infection stage in HSV seropositive mice, which implied that it could be an important factor to inhibit the tumor growth or eliminate the tumor directly.