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

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Abstract
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.
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要点】:本论文展示了人源化抗体huAR9.6在PDAC(胰腺导管腺癌)小鼠模型中减少肿瘤负担的效果,并在人源PDO模型中进行了验证。

方法】:通过皮下和原位PDAC模型,以及人源PDO模型进行抗体的抗肿瘤效果评估。

实验】:在皮下PDAC模型中,使用T3M4细胞种植在小鼠体内,第9天开始huAR9.6治疗(500 µg/25 g体重,每72小时一次,共4次),第19天结束实验。原位PDAC模型中,同样使用T3M4细胞种植,第18天开始huAR9.6及对照治疗,第28天结束实验。实验终点进行组织学染色和肿瘤大小测量。此外,使用huAR9.6处理PDAC患者来源的器官样细胞(PDO),并进行细胞增殖和信号传导研究。