Xenograft experiments testing hBU12-vcMMAE in models of NHL. In the subcutaneous xenograft models, treatment with hBU12-vcMMAE, or hBU12 or control compounds, was initiated when the average tumor volume per experimental cohort reached 100 mm3. Naked hBU12 failed to induce significant antitumor effects in the models shown (A; and data not shown). Mice were treated with hBU12-vcMMAE or control compounds at 1 and 3 mg/kg, q4dx4, via intraperitoneal administration. In all experiments, hBU12-vcMMAE significantly reduced tumor burden and improved survival compared with untreated mice or mice treated with hBU12 mAb or control-vcMMAE antibody. (A) Tumor growth curve of the follicular lymphoma cell lines DOHH2 treated with hBU12-vcMMAE at the dose and schedule indicated. (B) Tumor growth curve of the DLBCL cell line, DLCL2, treated with hBU12-vcMMAE at the dose and schedule indicated. (C) Survival of mice implanted with RS4;11 cells (ALL) via tail vein injections. Treatment of mice was initiated on day 7 after tumor implantation. (D) Survival curve of mice implanted with Nalm-6 cell (ALL) via tail vein injections. In the disseminated model, treatment was initiated on day 7 after tumor implantation. Data shown in panels A to D are from one representative of at least 2 independent experiments conducted. The graphs showing tumor volumes over time display median ± SEM of experimental cohorts of 7 to 10 animals. (E) Body weight changes of mice implanted intravenously with Nalm-6 tumor cells, with dosing starting on day 7 after tumor implantation (q4dx4), with the last dose administered on day 19. No significant changes in body weights between experimental cohorts by treatment were found in all xenograft experiments (data not shown). Data shown represent mean plus or minus SEM of experimental cohorts of 10 animals.
