Figure 4.

Vanadate Increases VSVΔ51 Efficacy in Resistant Syngeneic Tumor Models

(A–C) CT26WT, 4T1, DBT, 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. (A and B) Twenty-four and forty-eight hours post-infection, viral replication was monitored by IVIS. Representative bioluminescence images of mice are presented in (A), and quantification of luminescence is presented in (B). Scale represented in photons (n = 7–27; bars indicate mean; NS, no statistical significance; *p < 0.05, ***p < 0.001 by one-tailed t test; as compared to mock-treated condition). (C) Survival was monitored over time. Log rank (Mantel-Cox) test indicates that the combined treatment is significantly prolonged over PBS alone (CT26WT, p < 0.0001, n = 10–16; DBT, p = 0.0084, n = 4–7; 4T1, p = 0.0209, n = 6–8). (D and E) DBT tumor-bearing mice were treated intratumorally with the vehicle (PBS), 150 mg/kg of Vanadyl sulfate, or 80 mg/kg of BMOV and subsequently with 1 × 10⁸ PFU of oncolytic VSVΔ51 expressing firefly-luciferase intratumorally. Viral replication was monitored by IVIS; representative bioluminescence images of mice are presented in (D). (E) Quantification of luminescence (n = 4–5; error bars indicate SEM; *p < 0.05 by one-tailed t test; as compared to PBS-treated condition).