Figure 6.

EGFRvIII-binding antibodies reduce the growth of F98^EGFRvIII xenograft tumors in mice. NOD/scid mice were xenotransplanted by subcutaneous injection of 4 × 10⁶ F98^EGFRvIII cells mixed with 1 × 10⁷ human PBMC on day 0. Tandem diabody (TandAb) or vehicle was dosed intravenously as indicated 2 h post-tumor cell inoculation and on four subsequent days. Cetuximab was dosed intraperitoneal twice a week with 1 mg starting on day 0. (A) Dose-dependent tumor growth inhibition by EGFRvIII^Li3G30/CD3_x TandAb (containing the non-affinity optimized EGFRvIII-binding domain Li3G30). Statistical analysis (two-way repeated measures ANOVA with Bonferroni posttests) was performed and showed significant differences between the vehicle group and the 100-µg TandAb-treated group on day 38, day 41 (p < 0.05), day 43, and day 45 (p < 0.01). (B) Comparison of subcutaneous F98^EGFRvIII xenograft tumor growth retardation by EGFRvIII^Li3G30/CD3_x TandAb and EGFRvIII^A6/CD3_x TandAb containing an affinity matured anti-EGFRvIII domain (A6) at two dose levels each. This study was terminated after 27 days due to frequent tumor growth into the abdominal cavity and adjacent organs. Statistical analysis was performed and showed significant differences between the vehicle group and the 10-µg TandAb A6-treated group on days 6–22 (p < 0.05), or the 10-µg TandAb-treated group on days 8–20 (p < 0.05).