(A) The affinity of the monovalent m276 Fab for human, mouse, rat and monkey (cynomolgus) CD276 was determined using Biacore analysis.
(B, C) Cell viability assays were used to measure the activity of m276-MMAE against HT29 (B) and OVCAR3 (C) cells. To verify specificity, competition with unlabeled m276 was performed. Error bars in (B) and (C) = SD.
(D–H) Subcutaneous growth of colon HCT-116 (D), KM12 (E), HT29 (F), ovarian OVCAR3 (G), or orthotopic breast MDA-MB-231 (H) tumors. Treatments with vehicle, MMAE, m276, or m276-MMAE were initiated when tumors reached an average size of ~100mm3 and were administered on the days shown (green arrows). n = 10/group (DH). Error bars in (D) to (H) = SEM.
(I) Six OVCAR3 tumors that had relapsed following treatment with 3 mg/kg of m276-MMAE (biwk x 3.5) were retreated with 3 mg/kg (biwk x 3) starting on day 55 and then 10 mg/kg (biwk x 5) starting on day 76. Individual tumor measurements are shown.
See also Figures S3–S5.