AACR20 Poster 2768: New Bioluminescent Orthotopic KPC Murine Homograft Model for PDAC Drug Development

Development of a Bioluminescent Pancreatic Orthotopic KPC Model for Immuno-Oncology Drug Discovery

Yanrui Song, Phillip Shuzong Wang, Yinfei Yin, Henry Q. X. Li, Davy Xuesong Ouyang

Advanced preclinical models are needed for drug development in pancreatic ductal adenocarcinoma (PDAC), a cancer type with limited standard of care options. Orthotopic models provide a valuable preclinical tool, allowing cancer progression to be examined more accurately and drugs to be interrogated more faithfully.

We have previously established a Kras (G12D)/Trp53 null/Pdx1-cre (KPC) mouse homograft tumor model, to study innovative PDAC treatments. The mPA6115 KPC homograft model recapitulates human PDAC tumors in many aspects including a hostile tumor microenvironment (TME) and lack of response to a series of immune checkpoint inhibitors.

This poster details the development and characterization of an orthotopic bioluminescent version of the mPA6115 KPC homograft model, mPA6115-luc, compatible with optical imaging to facilitate preclinical evaluation of innovative treatments for PDAC.

Watch this Poster to Discover:

• Benchmark efficacy studies showing that mPA6115-luc is resistant to anti-PD-1 treatment
  
  
• Baseline immune profiling and IHC staining matching the parental model for enrichment of myeloid-derived suppressor cells and macrophages in the TME, obvious fibrosis, and angiogenesis
  
  
• Metastasis to the spleen and intestine found in nearly 50% of models following mPA6115-luc orthotopic engrafting

Watch the Poster Now!