Figure 3
Combination therapy for C57BL/6 mice injected in the flank with ID8-Vegf cells. Tumors from mice treated with Doxil with or without IL-18 were excised and weighed when the Doxil treated tumors reached the size of 600 mm3. Results are medians (50th percentile); error bars: interquartile range (25%-75%), (n = 9). (A) The Doxil-IL-18 combination treatment restricts significantly the tumor weight compared to the Doxil treated group (p = 0.034) (upper graph). Doxil was given at 4 mg/kg/dose for 4 weekly doses starting two weeks after tumor inoculation, while IL-18 was given at 10 μg daily for 50 days starting two days later. (B) The picture shows four tumors from mice treated with the combination of IL-18 and Doxil (upper row) and four tumors from mice treated with Doxil monotherapy (lower row). (C) The effect of mono- and combination therapy on tumor growth in vivo. C57BL/6 mice were injected i.p. with ID8-Vegf cells and subsequently treated. The chemotherapy treatment was started one week after the tumor challenge and IL-18 treatment 2 days later. In the Doxil-IL-18 combination group, 22% of the mice remained tumor-free 6 months after the tumor challenge while in the groups treated with either monotherapy the overall 6-month survival was 0% (untreated control: n = 9, IL-18: n = 9, Doxil: n = 8, Combination: n = 9). The tumor-free mice were rechallenged with ID8-Vegf cells injected s.c. and the tumors were rejected.