Efficacy of hBU12-vcMMAE in rituximab-resistant lymphomas. (A) Tumor growth curves of parental Ramos cells used to generate rituximab-resistant (R-Ramos) tumors. Tumor growth was significantly reduced by both rituximab (12 mg/kg, q4dx4) and hBU12-vcMMAE (3 mg/kg, q4dx4) treatment. The 2 peaks in the rituximab group were caused by the removal of 2 animals with tumors sizes exceeding 1000 mm³. (B) Tumor growth curves of rituximab-resistant R-Ramos tumors treated with hBU12-vcMMAE (3 mg/kg, intraperitoneally, q4dx4) or rituximab (12 mg/kg, q4dx4, intraperitoneally). hBU12 mAb failed to induce significant tumor growth delay in Ramos and R-Ramos (data not shown). Data shown in panels A and B are from one representative of 2 independent experiments, with 8 to 10 animals per group. (C) Flow cytometry to determine CD19 and CD20 expression levels on cells isolated from Ramos-P (sensitive) and R-Ramos (resistant) tumors. Comparable expression levels of both antigens were identified. (D) Western blot analysis of Bax, Bcl-XL, and Bak expression in rituximab-resistant Ramos cells (R-Ramos) or rituximab-sensitive, parental tumor cells (Ramos). Vertical lines have been inserted to indicate repositioned gel lanes.