Figure 4
In vivo efficacy. (a) Wild-type FcγR mice (10 per group): JIMT-1 cells implanted subcutaneously (s.c.) and monoclonal antibodies (mAbs) at 4 mg/kg administered five times at weekly intervals beginning at day 0. The first day of significant reduction in tumor size occurred at day 30 for both MGAH22 (P < 0.01) and RES120 (P < 0.01) compared with phosphate-buffered saline (PBS). (b) mCD16-/- mice (11 per group): JIMT-1 cells implanted s.c. and mAbs at 2 mg/kg administered six times at weekly intervals beginning at day 0. (c) mCD16-/- hCD16A+ mice (8 per group): JIMT-1 cells implanted s.c. and mAbs at 2 mg/kg administered six times at weekly intervals beginning at day 0. The first day of significant reduction in tumor sizes occurred at day 37 for MGAH22 compared with PBS (P < 0.001), at day 44 for RES120 compared with PBS (P < 0.01), and at day 61 for MGAH22 compared with RES120 (P < 0.05). (d, e) mCD16-/- hCD16A+ mice (10 per group): JIMT-1 cells implanted s.c. and tumors of approximately 200 mm3 allowed to form; RES120 (d) or MGAH22 (e) administered six times at weekly intervals beginning at day 6 at 0.01, 0.1, 1, or 10 mg/kg. The first day of significant reduction in tumor size occurred at day 32 for 1 or 10 mg/kg MGAH22 compared with PBS (P < 0.01), at day 41 for 10 mg/kg RES120 compared with PBS, at day 47 for 1 mg/kg MGAH22 compared with 1 mg/kg RES120 (P < 0.05), and at day 63 for 10 mg/kg MGAH22 compared with 10 mg/kg RES120 (P < 0.01). Data are presented as mean ± standard error of the mean. The first days of significant reduction in tumor sizes are indicated for MGAH22 or RES120 compared with vehicle (*) and for MGAH22 compared with RES120 (#). MGAH22, chimeric anti-HER2 monoclonal antibody with an optimized Fc domain; RES120, chimeric anti-HER2 monoclonal antibody with wild-type human immunoglobulin G 1 Fc domain.