Figure 3.

VD analogue (VD) potentiates Oncolytic virus (OV) replication and enhances survival in VD-responsive xenografts. Nude mice bearing flank tumors measuring an average of 160 mm³ of either VD-responsive HT29 or VD-non-responsive HCT116 were treated with IT PBS alone, IP PBS for 5 days + IT OV (CF33-hNIS-antiPDL1; 1e4 pfu), IP VD alone for 5 days (100 μg/kg), IP VD alone for 5 days + IT OV (CF33-hNIS-antiPDL1; 1e4 pfu). Tumor volumes are shown for HT29 (PBS n = 10; PBS + OV n = 8; VD n = 7; VD + OV n = 6) (A) and HCT116 (PBS n = 6; PBS + OV n = 9; VD n = 5; and VD + OV n = 8) (B) showing additive effects of VD in HT29 but not HCT116. Survival curves are shown for HT29 (C) and HCT116 (D) using humane endpoint of 1000 mm³ tumor volume for terminal event. 39 days following tumor treatment initiation, all mice were euthanized and tumor titers performed using standard plaque assay, showing increased viral replication in HT29 VD + OV combination group (E) but not HCT116 VD + OV combination group (F). Statistics for A & B = Welch’s t-test, error bars = SEM; * p < 0.05; Statistics for C & D = Log-rank (Mantel-Cox) test; Statistics for E & F = Mann-Whitney test * p < 0.05.