Fig. 4.

Anti-tumor effect of 1H5 in a colon cancer xenograft model. 6–8 weeks old female athymic nude mice were used. 5 million COLO205 cells per mouse were implanted (subcutaneous with Matrigel). Four groups were used (n = 4) for the experiment. When tumor volumes reached ~100 mm3, the four groups were injected as follows: (Group 1) sterile PBS (as a control). (Group 2) Irinotecan (i.p.) 20 mg/kg, three doses, once a week starting day 12. (Group 3) 1H5 (i.p.) at a dose of 30 mg/kg, biweekly (total 7 doses) starting day 7. (Group 4) Irinotecan (20 mg/kg, i.p., once a week starting day 12, total three doses) + continued 1H5 treatment (30 mg/kg, i.p., biweekly, total 7 doses). (A) Mean tumor volume ± 1 SD from day 7–35. 83 % tumor growth inhibition was recorded for the Group 4, treated with Irinotecan+ 1H5, 54 % for mAb alone (Group 3) and 48 % for Irinotecan alone (Group 2). No change in mouse weight or presence of diarrhea was observed in any of the groups. (B) Independent t test analysis showed significant difference in tumor volume reduction (day 35) between PBS and all treatments (with mAb and chemotherapy alone: p = 0.002; with combined treatment: p < 0.001). Significant tumor volume reduction differences were also observed between chemotherapy alone and combined treatment (p < 0.001), and between mAb treatment alone and combined treatment (p = 0.004). ANOVA with Dunnett multiple comparison post-hoc analysis likewise showed statistically significant tumor volume reduction between all treatment regimens vs. PBS control (all are p < 0.001), as well as between combination therapy and monotherapy (vs. chemotherapy p = 0.004; vs. mAB p = 0.011). In both analyses, the difference between mAb treatment and chemotherapy was not statistically significant. In the box and whiskers plot, the black horizontal lines indicate the average value, the top and bottom of the boxes, the interquartile range, and the whiskers, the range. Color coding on Panel B is the same as on Panel A.