Figure 4
The antitumor activity effected by IL-12 gene transfer increases in vivo when combined with cytosine deaminase/5-FC. (A) Renca tumors were established in BALB/c mice by s.c. inoculation of 1.5 × 105 cells. When the tumors reached 5–6 mm diameter, the animals were randomly divided into four treatment groups (n = 15 per group) and injected once intratumorally with (1) Ad.p35 (2.5 × 108 pfu) plus Ad.p40 (2.5 × 108 pfu) plus Ad.CD (5 × 108 pfu), or (2) Ad.p35 (5 × 108 pfu) and Ad.p40 (5 × 108 pfu), or (3) Ad.CD (1 × 109 pfu), or (4) Ad.GFP (1 × 109 pfu). Mice treated with Ad.CD were given 5-FC (400 mg/kg) intraperitoneally daily for 10 days. Graphic representations of mean tumor growth rates are shown. Bars indicate SD. (B) Mouse survival until day 42 was recorded. Mice were sacrificed and considered as death when tumor size exceeded 1.5 cm in long and short axes. The mean survival times (± SD) were 33.2 ± 10.4 days for (1) group, 27.2 ± 10.9 days for (2) group, 21.9 ± 9.1 days for (3) group, and 19.7 ± 7.1 days for (4) group. The difference between (1) and (2) groups was statistically significant (p < 0.0018) by Student's t test. The treatment outcome is summarized in Table 1. One animal in each of the groups treated with Ad.CD and Ad.GFP succumbed to toxicity, and two mice in the group treated with Ad.p35 plus Ad.p40 were excluded owing to peritoneal metastasis.