Fig. 4 DMF enhances VSVΔ51 therapeutic efficacy in syngeneic and xenograft tumor models. DMF enhances VSVΔ51 therapeutic efficacy in syngeneic and xenograft.

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Fig. 4 DMF enhances VSVΔ51 therapeutic efficacy in syngeneic and xenograft tumor models. DMF enhances VSVΔ51 therapeutic efficacy in syngeneic and xenograft tumor models. (A to D) CT26WT, B16F10, and HT29 tumor-bearing mice were treated intratumorally (IT) with the vehicle [dimethyl sulfoxide (DMSO)] or DMF [50 mg/kg (B16F10) or 200 mg/kg (CT26WT and HT29)] for 4 hours and subsequently injected with 1 × 108 PFU of oncolytic VSVΔ51 expressing firefly luciferase or the vehicle [phosphate-buffered saline (PBS)] intratumorally. The treatment was administered two or three times, as indicated by arrows in (C). Twenty-four hours post-infection (hpi), viral replication was monitored. (A) Representative bioluminescence images of mice. (B) Quantification of luminescence in photons/s (n = 10 to 18; horizontal lines indicate means; **P < 0.01, two-tailed t test, as compared to VSVΔ51-infected condition; dashed lines represent average background intensity). (C) Tumor volume (n = 9 to 15; data are mean ± SEM; SD values are indicated in table S1; *P < 0.05, **P < 0.01, ***P < 0.001, two-way ANOVA, comparing DMF + VSVΔ51 to DMSO alone). (D) Survival was monitored over time. Log-rank (Mantel-Cox) test indicates that the combined treatment significantly prolonged survival over VSVΔ51 alone (CT26WT: n = 10 to 13, P = 0.0008; B16F10: n = 9 to 14, P = 0.0039; HT29: n = 10 to 15, P = 0.0003). (E) Tumor volume and survival were monitored after reimplantation of CT26WT in cured and naïve mice from (D) (n = 3 to 5, mean ± SD). (F) Tumor volume was monitored after implantation of 4T1 cells in CT26WT-cured and naïve mice (n = 3, mean ± SD). Mohammed Selman et al., Sci Transl Med 2018;10:eaao1613 Published by AAAS