Although, there is a trend toward reduced CD4+ T cells in the anti-CTLA-4-treated group and a trend toward reduced Tregs in the anti-PD-1 treated group relative to isotype control, no other immune changes are observed. Despite checkpoint inhibitors alone having no apparent activity in the Pan02 model, there are published reports of checkpoint inhibitor activity in Pan02 tumors with radiation3 or a costimulatory agonist anti-CD40 antibody.4 Importantly, anti-PD-L1 strongly synergized with both anti-CD40 and radiation in those studies indicating that while Pan02 tumors are refractory to single agent checkpoint inhibitors, checkpoint inhibition can promote activity of combination partners.
Contact us to speak with one of our scientists to see how Pan02 or one of our other syngeneic models can be used for your next immuno-oncology study.
1Corbett TH et al., Induction and Chemotherapeutic Response of Two Transplantable Ductal Adenocarcinomas of the Pancreas in C57BL/6 Mice. Cancer Res. 1984, Vol. 44: 717-726.
2Wang Y et al., Genomic Sequencing of Key Genes in Mouse Pancreatic Cancer Cells. 2012. Curr Mol Med. Vol. 12(3): 331–341.
3Azad A et al., PD-L1 blockade enhances response of pancreatic ductal adenocarcinoma to radiotherapy. 2017. EMBO Mol Med. Vol 9: 167–180.
4Luheshi NM et al., Transformation of the tumour microenvironment by a CD40 agonist antibody correlates with improved responses to PD-L1 blockade in a mouse orthotopic pancreatic tumour model. 2016. Oncotarget. Vol. 7(14): 18508-18520.
Note: Please note that all animal care and use was conducted according to animal welfare regulations in an AAALAC-accredited facility with IACUC protocol review and approval.