Fig. 6

Humanized anti-sCD146 antibody, mucizumab, significantly reduces tumor growth in two different in-vivo models and displays complementary effects with bevacizumab. Tumor volume was measured in 20 athymic nude mice subcutaneously injected with U87 cells after treatment with IgG, bevacizumab (Avastin), mucizumab or bevacizumab + mucizumab. 5 mice were used in each group. Representative images of tumors and their weight are shown (a). 40 mice were orthotopically injected with U87 cells and treated with IgG, Avastin, mucizumab or bevacizumab + mucizumab. 10 mice were used in each group. Tumor volume was estimated based on immunohistochemical staining of human CD146 in serially cut mice brain sections (b). Tumor cell dissemination across all the brain was also determined. Red arrows show disseminated cells (c). Expression of human specific CD146 and MAX proteins in total brain lysate was determined in each group (d). In each group, imaging was performed in 6 representative mice orthotopically bearing U87 tumors using PET-scan after 86 Ga-RGD injection. Results were expressed as ratio of radioactivity between right (RH) and left (LH) hemispheres (e). Representative images are shown. *p < 0.05, **p < 0.01, ***p < 0.001, experimental vs control