Figure 3.
Vaccinia virus enhances vesicular stomatitis virus expression into human in vivo tumor. (a) HT29 subcutaneous xenograft tumor models were established in nude mice. Group received VVDD or VVΔB18R-eGFP (1 × 106 pfu) and 2 days after, VSVΔ51-luciferease (1 × 107 pfu) was also injected intravenously. Viral replication at tumor site was imaged using in vivo imaging system 6 days after VSVΔ51 injection for GFP and luciferase. Three representative mice per group are presented. (b) In vivo tumors were homogenized and titrations were performed for each mouse of the groups (VSVΔ51 and VVΔB18R/VSVΔ51 N = 5, VVDD/VSVΔ51 N = 9). Bars correspond to SEM. t-Test between VVDD/VSVΔ51 and VVΔB18R/VSVΔ51 groups. (c) Tumor frozen sections were used for IgG, anti-VSV and caspase 3 immunohistochemistry analysis. (d) HT29 model was established in nude mice. 10 days later, viruses were injected as previously described. Size of tumor was monitored for each groups (N = 4) and average tumor volumes relative to D14 are shown. Bars correspond to the SEM. **P < 0.05 [analysis of variance (ANOVA) comparing VVDD/VSV to VVDB18r/VSV]. (e) 4T1 (1 × 105 cells) subcutaneous graft tumor models were established in immunocompetent mice. Six days later (palpable tumors) animals were treated by intravenous injection with VVDD (1 × 107 pfu/dose) and/or VSV (1 × 108 pfu/dose). Size of tumor was monitored for each groups (N = 10) and average tumor volumes relative to D6 are shown. Bars correspond to the SEM. **P < 0.05 (ANOVA comparing VVDD/VSV to VSV; VSV to PBS or VVDD). Similar results were obtained in two other independent experiments (N = 7) with 4T1 (3 ×105 cells). (f) Cumulative survival rate of 4T1 experimentation described in e was evaluated according to treatment groups. **Kaplan–Meier statistic comparing VSV group to the combination viruses group, LogRank = 6.3, P value = 0.0121. Similar results were obtained in two other independent experiments (Ntotal = 17).