Figure 6

MIF-specific inhibition reduces colon cancer in vivo. (A) ISO-1 inhibits the bioactivity of serum MIF in mice. Following transplantation of CT26 tumor cells, mice were divided into three groups and treated twice weekly with saline, vehicle (5% DMSO), or the MIF-specific inhibitor ISO-1 (20 mg/kg in 5% DMSO) intraperitoneally. As a surrogate measure of MIF inhibition, the serum was collected and analyzed for MIF bioactivity as determined by in vitro tautomerase activity at d 28. (B and C) ISO-1 inhibits colorectal tumor burden as assessed by measuring either the tumor volume (B) or the tumor weight at d 28 of treatment (C). (D) ISO-1 inhibits angiogenesis as assessed by quantitating the number of microvessels by CD31 immunostaining. (E) Neutralizing anti-MIF antibodies inhibit colorectal tumor burden as assessed by measuring the tumor weight at d 28. Mice were given transplants of CT26 tumor cells as above and divided into two groups. Treatment consisted of either anti-MIF antibodies or isotype-matched control IgG, administered every other day, intraperitoneally. Histograms represent the mean ± SEM. **P < 0.01, ***P < 0.001 between anti-MIF therapy and all control groups.