Figure 4.
Inhibiting tumor growth by targeting tumor endothelial vimentin. (A) Tumor growth curves of LS174T human colon carcinoma tumor xenografts in nude mice, treated with vehicle, IIB5 anti-BrdU isotype-matched control antibody (10 mg/kg), or RV202 antivimentin antibody (10 mg/kg and 1 mg/kg). Antibodies were administered intraperitoneally every 3 days for a period of 12 days. A dose-dependent inhibition of tumor growth is evident in mice treated with antivimentin antibody (1 mg/kg, **P < .001; 10 mg/kg, **P < .001), whereas treatment with the isotype control antibody did not show inhibition of tumor growth (IIB5; 10 mg/kg, P = .661). (B) Immunohistochemical staining of LS174T tumor xenografts in mice with CD31 (i) and antivimentin antibody RV202(ii) show that vimentin expression is restricted to the endothelium. Microvessel staining with phycoerythrin-labeled CD31 antibody in control mice (iii), isotype control antibody–treated mice (iv), RV202 (1 mg/kg per treatment) (v), and RV202 (10 mg/kg per treatment)–treated mice (vi). (C) Quantification of microvessel density (±SEM) was assessed digitally (**P < .001; Student t test). (D) Body weight of mice during treatment, indicating absence of toxicity. (E) Detection of treatment antibodies targeted to the tumor endothelium. Mouse antibodies were detected (green fluorescence) in mice treated with saline (i), isotype control antibody (ii), RV202 (1 mg/kg per treatment) (iii), and RV202 (10 mg/kg per treatment) (iv). Endothelial cells are stained with phycoerythrin-labeled anti-CD31 antibody in red. Yellow indicates colocalization.