Superior antitumor efficacy of GA101 compared with rituximab in human lymphoma xenograft models. (A) Established subcutaneous SU-DHL4 (DLBCL) tumors (250 mm3; n = 10 per group) were treated with 1 mg/kg (dotted lines), 10 mg/kg (short dashed lines), and 30 mg/kg (solid lines) GA101 (every 7 days, 3 times, intravenously; black) compared with identical doses of rituximab (dark gray) and vehicle control (light gray). GA101 treatment resulted in a dose-dependent inhibition of tumor growth that was superior to that of rituximab. A total of 10 of 10 mice showed complete tumor remission and 9 of 10 mice showed long-term survival (> 90 days; cure) after treatment with 30 mg/kg GA101; and 1 of 10 mice showed complete tumor remission after treatment with 10 mg/kg GA101. In the rituximab-treated groups, no complete tumor remission was observed. Data are mean ± SD. (B) Established subcutaneous SU-DHL4 xenografts (n = 10 per group) were treated with rituximab (30 mg/kg every 7 days, intravenously) as single-agent first-line therapy (days 22-35). Xenografts progressing under first-line rituximab treatment (30 mg/kg every 7 days) were subsequently randomized and reassigned to the following treatment groups with weekly dosing (from days 35-60): vehicle (gray curve), rituximab (30 mg/kg every 7 days; dark gray curve), or GA101 (30 mg/kg every 7 days; black curve). SU-DHL4 tumor progression (advanced xenografts; 750 mm3) was effectively controlled through the use of GA101 as a second-line therapy, whereas rituximab treated-tumors remained refractory. (C) Treatment of the aggressive orthotopic disseminated Z138 (MCL) model was initiated 29 days after intravenous injection of tumor cells (n = 10 per group). Treatment with 10 mg/kg GA101 (every 7 days, 6 times, intravenously; black line) resulted in increased overall and median survival, compared with 10 mg/kg rituximab treatment (dark gray line; P < .008) and vehicle control (light gray line). ↑ indicates the treatment time points.
