Figure 4. Combinations of low doses of the AdΔΔ mutant and docetaxel inhibited tumor progression in human prostate carcinoma xenografts in nude mice.

A) Animals with DU145 subcutaneous tumor xenografts were treated with PBS (phosphate buffered saline; filled circle), the AdΔΔ mutant at 1×10⁹vp (intratumoral injections on day 1, 3, and 5) with and without docetaxel at 5mg/kg (intraperitoneal administration on day 2 and 8) (open and filled squares respectively) or docetaxel 5mg/kg alone (D5; triangle) and tumor growth was monitored. *p<0.001 for treatments compared to either single agent treatment and viral mutant compared to untreated animals. Significance determined by one-way Anova analysis. B) Animals with PC3 subcutaneous tumor xenografts were treated as above with the indicated suboptimal doses 1×10⁹vp (dl312; open circles, and AdΔΔ; filled diamond) and docetaxel at 10mg/kg (D10; open triangle) or combination of AdΔΔ and docetaxel (open square). Median time to tumor progression (tumor volume >500μl) was determined by Kaplan-Meier survival analysis, 6-10 animals per group. *p<0.002 for combination treated compared to single agent groups. C) Viral genome amplification in DU145 tumors after intratumoral administration of virus on day 0, treated as indicated for 3 and 10 days. Total DNA was extracted and quantified by qPCR using specific hexon primers. Data averaged from 3 tumors/group, analysed in triplicates, and expressed as hexon DNA copies/5ng total DNA ±SD. Right panel: Viral amplification in DU145 tumors for the AdΔΔ mutant with and without simultaneous docetaxel administration at 5mg/kg. D) Viral hexon expression in DU145 tumor sections after intratumoral injection of 1×10⁹vp of the respective mutant. One group treated with the AdΔΔ mutant and docetaxel at 10mg/kg. Three tumors were evaluated from each treatment group and analysed for expression of hexon 10 days after viral treatment, magnification 200x.