Building Kras (G12D)/Trp53 null/Pdx1-cre (KPC) Mouse Homograft Tumor Models for the Efficacy Evaluation of Combinatory Immunotherapies
Yanrui Song, Benqi Liu, Annie Xiaoyu An, Likun Zhang, Jie Cai, Henry Qixiang Li, and Davy Xuesong Ouyang
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult to treat cancer types, with very few standard of care options available. The success of immune checkpoint inhibitors in other solid tumors has led to clinical trials in PDAC. However, single agent success has been limited, and investigators are now keen to test combination regimens, therefore requiring appropriate immunocompetent models for preclinical testing.
KPC models recapitulate human PDAC tumors in many aspects including morphological small ductal tumors with enriched stromal contents, key features of the PDAC immune microenvironment, and a lack of response to a range of chemotherapies and checkpoint inhibitors including anti-PD-1 and CTLA-4 antibodies.
However, the parental KPC model is difficult to use for pharmacological studies due to the spontaneous nature of tumor onset and progression. CrownBio has therefore generated a transplantable KPC tumor model by passaging the primary tumor subcutaneously in C57BL/6 mice, which retains morphological similarity to human PDAC, and is more suitable for in vivo pharmacological research.
Read this Poster to Discover:
- That KPC GEMM and KPC homograft models recapitulate key aspects of human PDAC, including histopathology, immune profile, and drug response, therefore offering an ideal model platform for PDAC in vivo pharmacological research
- That using orthotopic KPC homograft models, significantly extended survival of tumor bearing mice is observed following treatment with a novel immunotherapeutic
- Initial combination regimen efficacy study data with immunomodulatory agents and immune checkpoint antibodies i.e., BTKi and PD-L1 treatment, with further combinatory strategies ongoing