Fig. 8: 441 equally effectively controls growth of N-87 xenograft tumors in mice, compared to mAb combinations.

a 441 and the mAb combinations showed powerful reduction of tumor volume under treatment (441 n = 6, TZB n = 5, hA21G n = 7, TZB + PZB n = 7, TZB + hA21G n = 6, PBS n = 7, error bar SEM) in female SCID beige mice with subcutaneous N-87 tumors. b Tumor volumes were analyzed on day 42. Single mAb treatments were significantly different to 441. 441 was non-inferior to the mAb combinations (441 n = 6, TZB n = 5, hA21G n = 7, TZB + PZB n = 7, TZB + hA21G n = 6, box plot with min/max whiskers, two-sided Brown-Forsythe and Welch’s ANOVA with Dunnett’s 3T multiple testing correction, adjusted p value 441 vs. hA21G < 0.0001; 441 vs. TZB + hA21G 0.0322; 441 vs. TZB < 0.0001, 441 vs. TZB + PZB 0.0455). c After the first three interventions, scouts were sacrificed and their tumors analyzed by immunohistochemistry. Effective treatments showed significantly reduced HER2 and pHER2 levels (n > 3000 cells, two-sided Kruskal–Wallis test with the Dunn’s multiple comparisons test). d Further histology revealed that loss of the tumor driver HER2 reduced the number of Ki67-positive cells (n > 20000 total cells), induced apoptosis (n > 40,000 total cells), but showed no necrosis compared to the PBS sample. e All tumors eventually did outgrow. Evaluation of remaining tumor mass 8 weeks post the last treatment revealed significantly more necrotic tissue for 441-treated tumors, while numbers of Ki67- and caspase-3-positive cells were equal compared to combination treatments (n = 3–5 mice with each >20,000 cells analyzed, two-sided ANOVA with Dunnett’s multiple comparisons test). Source data are available in the Source Data file.