Antilymphoma effects of hBU12-vcMMAE against subcutaneously implanted, rituximab-resistant Raji tumors. (A) Parental Raji tumors were treated with rituximab (12 mg/kg, 3 times weekly), hBU12-vcMMAE (q4dx4), or control-vcMMAE compound. (B) Raji-2R tumors treated with hBU12-vcMMAE at 1 or 3 mg/kg, q4dx4 or a control conjugate. Nine durable regressions in 10 tumor-bearing mice were obtained after hBU12-vcMMAE treatment, whereas rituximab (12 mg/kg, 3 times weekly for 2 weeks) did not significantly impact tumor growth. (C) Effect of hBU12-vcMMAE treatment (q4dx4) on growth of subcutaneously implanted Raji-4RH tumors. For comparison, control groups were either untreated or treated with a control ADC or with rituximab (12 mg/kg, 3 times weekly for 2 weeks). Data shown in panels A to C are from one representative of 2 independent experiments, with 8 to 10 animals per group. (D) Western blotting analysis of Bax, Bak, and Bcl-XL in cell lysates prepared from Raji-2R or Raji-4RH cell treated with control mAb or rituximab and compared with parental, Raji-P cells and Ramos. Our data confirm the down-regulation of Bax, Bak, and Bcl-XL in rituximab-resistant Raji cell lines reported previously.²⁴