Establishment of Kras (G12D)/Trp53 null/Pdx1-cre (KPC) Mouse Homograft Tumour Models to Facilitate Efficacy Evaluation of Combinatory Immunotherapies
Yanrui Song, Benqi Liu, Annie Xiaoyu An, Likun Zhang, Jie Cai, Henry Qixiang Li, and Davy Xuesong Ouyang
Preclinical, immunocompetent models are needed for immunotherapy drug development in pancreatic ductal adenocarcinoma (PDAC). This cancer type shows resistance to standard of care therapies and single agent immune checkpoint inhibitors, leaving combination immunotherapies as the next treatment route researchers would like to assess.
KPC (Kras (G12D)/Trp53 null/Pdx1-cre) GEMM are available, which recapitulate many features of human PDAC such as morphological small ductal tumours with enriched stromal contents, key features of the PDAC immune microenvironment, and importantly, a lack of treatment response. However, GEMM in general are difficult to use for efficacy studies, with spontaneously developing tumours and cost restrictions.
To overcome these limitations, CrownBio has developed a transplantable murine KPC homograft tumour model by passaging the primary GEMM tumour subcutaneously in C57BL/6 mice. This model preserves the morphological similarity to human PDAC, and is more suited to in vivo efficacy and proof of concept studies.
Read this Poster to Discover:
- The development of a series of murine homograft tumour models (including a KPC homograft) carrying various mutations highly relevant to human cancer and representing a novel platform for cancer immunotherapy development
- That KPC homograft subcutaneous and orthotopic tumour models recapitulate key aspects of human PDAC, including histopathology, immune profile, and drug response, therefore providing an ideal model for PDAC in vivo immunotherapy research
- That studies using the orthotopic KPC homograft model have shown significantly extended survival of tumour bearing mice when treated with a novel immunotherapeutic, with further I/O combination studies ongoing