Figure 6
CD gene transfer followed by 5-FC treatment increases the antitumor effectiveness of IL-12 gene transfer. (A) Mice with tumors were established by subcutaneous inoculation of 1.5 × 105 cells of Renca. The experimental animals in which tumors reached a diameter of about 5 mm were randomly divided into 4 treatment groups (n = 7 per group) and injected once intratumorally (day 0) with Ad.IL-12 (5 × 108 pfu) plus Ad.CD (5 × 108 pfu), or 1 × 109 pfu of Ad.IL-12, or Ad.CD, or Ad.GFP. Mice treated with Ad.CD were given intraperitoneal 5-FC (400 mg/kg) daily for 10 days. Tumor growth was measured at intervals of three days until day 21. Graphic representations of mean tumor growth rates are shown. (B) and (C) Renca tumor-bearing mice were divided into two groups (n = 8 per group), which received single intratumorally injections (day 0) of Ad.IL-12 (5 × 108 pfu) plus Ad.CD (5 × 108 pfu) or Ad.IL-12 (5 × 108 pfu) plus Ad.GFP (5 × 108 pfu). Mice in both groups were given intraperitoneal 5-FC (400 mg/kg) daily for 10 days. Tumor growth was measured at the indicated times until day 25. Graphic representations of mean tumor growth rates are shown (B). Mouse survival until day 88 was recorded (C). The mean survival times (± SD) were 80.5 ± 20.8 days for the Ad.IL-12 plus Ad.CD/5-FC group and 67.3 ± 28.3 days for the Ad.IL-12 plus Ad.GFP/5-FC group. The difference between these mean survival times was statistically significant (p < 0.0368) by Student's t test.