Preclinical data

Female SCID beige mice, age 8 weeks, were housed in specific‐pathogen‐free conditions according to committed guidelines (GV‐Solas, Felasa, TierschG) and injected with a suspension of 3 × 10⁶ KPL‐4 tumor cells into the right, penultimate, inguinal mammary fat pad. Treatment started 38 days after tumor cell injection, when tumors had reached a mean size of 70 mm³, and mice were randomized into control (omalizumab), bevacizumab treatment, and vanucizumab treatment groups with 10 mice per group.

Bevacizumab is an anti‐VEGF antibody, vanucizumab is a bispecific anti‐VEGF/anti‐Ang‐2 antibody that neutralizes both ligands, and omalizumab was included as an isotype control. Each antibody was administered via i.v. injection at a dose of 10 mg/kg, once per week, starting 38 days after inoculation for a total of 5 weeks.

Tumor volume, T, was calculated using the formula T=length×width22, where the length and width of the tumor were the longest and shortest dimensions of the tumor lying at 90 ° to the longest, respectively. These measurements were taken twice per week for the treatment period, resulting in a total of 10 tumor size measurements per animal. The data are presented in Figure ​11.

Individual tumor size data for (a) control tumors (n = 10), (b) bevacizumab treated animals (n = 10), (c) vanucizumab treated animals (n = 10), (d) mean tumor volume of individual groups. Treatment times are shown by vertical arrows in plots (b–d).