Figure 5.

Vanadate/VSVΔ51 Co-treatment Triggers T Cell Infiltration and Antitumor Immunity

(A–C) CT26WT tumor-bearing mice were treated intratumorally with the vehicle (PBS) or 40 mg/kg of vanadate (pH 7.4 prepared from orthovanadate) for 4 hr and subsequently treated with 1 × 10⁸ PFU of oncolytic VSVΔ51 expressing firefly-luciferase, intratumorally. The vanadate + VSVΔ51 group was divided into two groups, High and Low responders (HR and LR), based on median tumor size 10 days post-treatment, as shown in (B). Viral replication was monitored 24 hr post-infection; quantification of luminescence is presented in (C) (n = 5). Tumor volume 10 days post-treatment is shown in (B) (n = 5). (A) Percentage of CD45⁺ cells; CD3⁺ cells of total CD45⁺ cells; IFNγ-expressing CD8⁺ cells in each tumor was quantified by flow cytometry, 10 days post-treatment (n = 4–5; error bars indicate SEM; *p < 0.05, **p < 0.001, ***p < 0.0001, by one-way ANOVA). (D) Survival was monitored after re-implantation of CT26WT in cured and naive mice from Figure 4C (n = 3–5). (E) Immunocompetent mice and (F) nude mice bearing the CT26LacZ tumor were treated intratumorally with the vehicle (PBS) or 40 mg/kg of vanadate for 4 hr and subsequently treated with 1 × 10⁸ PFU of oncolytic VSVΔ51 expressing firefly-luciferase intratumorally. Log rank (Mantel-Cox) test indicates that survival in the combined treatment is significantly prolonged over VSVΔ51 alone in the immunocompetent mouse model alone (immunocompetent mice, p = 0.0506, n = 6–8; nude mice no statistical significance, n = 4–10). (G) Schematic representation of treatment schedule for bilateral DBT tumors. (H) Representative bioluminescence images of mice are presented. (I) Growth of treated (right flank) and distant (left flank) DBT tumors (n = 4–7).