The animal experimental protocol was approved by the Institutional Animal Care and Use Committees of Emory University. In brief, 4×106 Tu212 and 2×106 SCC47 cells (1:1 in matrigel) were injected subcutaneously into female nude mice (athymic nu/nu, Taconic, NY) aged 4 to 6 weeks. Mice were randomly divided into 6 groups after tumor formation: PBS control, cetuximab 6.25μg/dose, MM-121 300μg/dose (MM-121.LD), MM-121 600μg/dose (MM-121.HD), combination with low dose MM-121 (comb. LD) and combination with high dose MM-121 (comb. HD) (n=7 for each treatment group). Doses were chosen based on previous studies (19 (link), 25 (link)). Drugs were given by intraperitoneal injection (I.P.) twice a week. Tumor volume and bodyweight were measured three times a week. Tumor volume was calculated using the formula: V= π/6×larger diameter ×(smaller diameter)2 as reported previously (25 (link)). Major organs were harvested for toxicity evaluation by hematoxylin and eosin (H&E) staining.