A Combinatorial Effect of Immune Checkpoint Inhibitors and CD40 Agonistic Antibody in Murine Pancreatic Cancer Model.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognoses of all cancer types. Immune checkpoint inhibitors (ICIs) are currently not indicated for patients with PDAC except for those with high microsatellite instability. In this study, we developed an immunocompetent orthotopic transplant mouse model with Kras and Trp53 mutations, characterized by high fibrosis and an immunosuppressive tumor microenvironment, closely mimicking human PDAC lesions. This model provides a robust platform for investigating strategies for improving ICI efficacy. We observed that ICI monotherapy yielded minimal efficacy, whereas anti-CD40 agonist antibody (aCD40) monotherapy prolonged survival despite its low impact on primary tumor volume. Moreover, ICIs + aCD40 combination therapy not only extend

SUBMITTER: Ichikawa J 

PROVIDER: S-EPMC12775589 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature