Development Of A Transgenic Porcine Model Of Pancreatic Adenocarcinoma

Introduction Five-year survival from pancreatic cancer (PC) is less than 10% and has not changed substantially in decades. Current murine models may not adequately mimic human PC which may contribute to the lack of progress in survival. We attempted PC induction in transgenic swine with the goal of creating a more clinically-relevant model. Methods Transgenic Oncopigs (n=8, male, 5 mo; wt 37.2 kg, nsrrc.missouri.edu; somatic LSL cassette TP53R167H and KRASG12D) were injected via laparotomy with AdCre (1010 vp/uL) ± IL-8 (5 ng/mL; for adenoviral entry into epithelia and local inflammation) into the main pancreatic duct (MPD; via duodenotomy) or duct to the isolated pancreatic connecting lobe (CL). Wildtype (WT) control pigs (n=6, male, 5mo; wt 45kg UNL Mead) were also injected via laparotomy with either normal saline (NS), AdCre, or AdCre + IL-8 (5ng/mL) into the CL. Subjects were necropsied after ≤10 wk, followed by histology (Table 1.) Results Subject Oncopig 1 died prematurely from gastric perforation (tissue NA); subjects Oncopigs 3, 4, 5, 7 were euthanized early due to illness (manifested as decreased feeding, decreased stooling, abdominal distension). Necropsy revealed fulminant hemorrhagic pancreatitis which resulted in gastric outlet obstruction. Subject Oncopig 7 also was noted to have peritoneal carcinomatosis. Subjects Oncopigs 2, 6, 8 were clinically well at euthanasia. Subjects Oncopigs 2, 6, 8 did not have any tumor on HE necropsy showed no gross evidence of pancreatitis. HE 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6131.