Supplementary Figure S6 from Structural Basis for Multivalent MUC16 Recognition and Robust Anti-Pancreatic Cancer Activity of Humanized Antibody AR9.6

Fig. S6. huAR9.6 reduces tumor burden in models of PDAC. (A) Schematic of subcutaneous PDAC model using T3M4 cells implanted in athymic nude mice (n=5). On day 9 post implantation, mice were randomized to two treatment groups: vehicle (PBS) and huAR9.6 (500 µg/25 g bodyweight, i.p. every 72 h) for 4 doses. At the experimental endpoint (day 19), mice were euthanized. (B) Hematoxylin and eosin (H&E) staining, Ki67 staining and CD31 staining of formalin-fixed paraffin embedded (FFPE) subcutaneous tumor tissues (n=5) treated with vehicle and huAR9.6. Scale bar 100 µm. (C) Schematic of orthotopic PDAC model using T3M4 cells implanted in athymic nude mice. On day 18 post implantation, mice were randomized to three treatment groups (n=7 per group): vehicle (PBS), isotype control huIgG and huAR9.6 (500 µg/25 g bodyweight, i.p.) for 4 doses. At the experimental endpoint (day 28), mice were euthanized. (D) Differences in tumor size from the three treatment groups. (E) Schematic of PDAC patient-derived organoid (PDO) development and treatment (n=3) with huAR9.6 (40 µg/mL for 24 h) and isotype control huIgG and subjected to further studies with cell proliferation and signaling. (F) Immunofluorescent staining for MUC16 with huAR9.6 on primary human PDAC tissue and matched PDO. Scale bar 50 µm.