biostudies-literatureMuth STBristol-Myers SquibbNational Cancer InstituteNCI NIH HHS99-108https://www.ebi.ac.uk/biostudies/studies/S-EPMC7779747biostudies-literatureUnknown499Pancreatic ductal adenocarcinoma(PDAC) is resistant to the PD-1/PD-L1 blockade therapy. Previously, the combination of PD-1 blockade and vaccine therapy was shown to have a modest antitumor activity in murine models of PDAC. We used a murine syngeneic model of metastatic PDAC to identify, among multiple T cell modulators tested, which therapeutic agents in combination with the GVAX cancer vaccine and an anti-PD-1 antagonist antibody(αPD-1) are able to improve the survival. We found that an anti-CD137 agonist antibody(αCD137) most significantly improved survival in the mouse PDAC model. Moreover, αPD-1 and αCD137 together in combination with vaccine therapy more significantly increased the expression of costimulatory molecules CD137 and OX40 on CD4+PD-1+ and CD8+PD-1+ T cells comparing to αCancer lettersCD137 agonist-based combination immunotherapy enhances activated, effector memory T cells and prolongs survival in pancreatic adenocarcinoma.PMC7779747P30 CA006973T32 CA009071R01 CA197296T32 CA126607R01 CA169702K23 CA148964P50 CA062924Blair ABSaung MTZheng LThomas DLMuth STHenderson MGfalseCD137 agonist-based combination immunotherapy enhances activated, effector memory T cells and prolongs survival in pancreatic adenocarcinoma.Pancreatic ductal adenocarcinoma(PDAC) is resistant to the PD-1/PD-L1 blockade therapy. Previously, the combination of PD-1 blockade and vaccine therapy was shown to have a modest antitumor activity in murine models of PDAC. We used a murine syngeneic model of metastatic PDAC to identify, among multiple T cell modulators tested, which therapeutic agents in combination with the GVAX cancer vaccine and an anti-PD-1 antagonist antibody(αPD-1) are able to improve the survival. We found that an anti-CD137 agonist antibody(αCD137) most significantly improved survival in the mouse PDAC model. Moreover, αPD-1 and αCD137 together in combination with vaccine therapy more significantly increased the expression of costimulatory molecules CD137 and OX40 on CD4+PD-1+ and CD8+PD-1+ T cells comparing to α2021-01-01T00:00:00Z2021 Feb2026-05-09T03:21:23.646Z2025-04-04T22:15:37.746ZS-EPMC77797473327126410.1016/j.canlet.2020.11.041