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Abstract 930: Novel orthotopic pancreatic cancer cell lines derived from B6-KPC mice


 Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. B6-KPC mice ( LSL-KrasG12D/+, LSL-Trp53R172H/+, Pdx1-Cre) generate spontaneous PDAC which could recapitulate the pathogenesis and genomic features of human PDAC. Although B6-KPC model is a wildly used for the exploration of the mechanisms of PDAC, some drawbacks of the model, such as long time for tumorigenesis, individual variation and difficulties in tumor observation, limit its application in cancer therapy. It is necessary to develop the pancreatic tumor cell lines from these models. In this study, we successfully established and well-characterized the luciferase-labled cell line mPAKPC-Luciferase. This cells carried the KrasG12D and Trp53R172H mutation. The orthotopic mPAKPC-Luciferase tumor model was well established by implanting tumor cell line into pancreas of B6 wild type mice and the tumor growth was traced by in vivo imaging. Moreover, Gemcitabine or combined with CD40 agonist presented significant tumor growth inhibition in B6 bearing mPAKPC-Luciferase orthotopic mouse models. While anti-PD1 or anti-OX40 had no anti-tumor effects in this model accordance with the low T cell infiltration of mPAKPC modle as a “cold” tumor. In addition, the immune profiling of this cell line showed highly expressed of potential therapeutic targets, including Claudin 18.2, CD47, CD73. Thus, mPAKPC-Luciferase cell lines are valuable models for the PDAC preclinical therapies.
 Citation Format: Fang Zhu, Cunxiang Ju, Hongyan Sun, Weiwei Yu, Chao Ju, Shuai Li, Yunlong Jiang, Dongjing Jia, Steve Smith, Zhiying Li, Jing Zhao, Xiang Gao. Novel orthotopic pancreatic cancer cell lines derived from B6-KPC mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 930.