Abstract B003: Oncolytic VSVd51-LIGHT and folfirinox chemotherapy increases anti-tumor immune response in pancreatic ductal adenocarcinoma

Abstract The immunosuppressive tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) is a major factor that limits the therapeutic effect of immunotherapy and chemotherapy in PDAC patients. A promising approach is the use of oncolytic viruses (OVs), particularly the vesicular stomatitis virus (VSVd51), which has been shown to have an increased cytotoxicity on PDAC cells while sparing healthy cells. Additionally, enhancing OVs with immune-stimulating cytokines has shown great promise in cold tumors such as PDAC because of its ability to potentiate antitumor immune responses. Our study aims to modulate the PDAC TME using an oncolytic virus armed with the pro-inflammatory cytokine tumor-necrosis factor superfamily member 14 (VSVd51-LIGHT). In our orthotopic mouse model of PDAC, murine pancreatic KPC cancer cell lines were implanted orthotopically into the pancreas of immune-competent mice. Mice were treated intraperitoneally with VSVd51-LIGHT, Folfirinox, or a combination of both therapies. Notably, a synergistic effect was observed when VSVd51-LIGHT was combined with chemotherapy, extending the median mice survival from 34 to 42 days. In parallel, the antitumor immune response was assessed using flow cytometry and IFNγ ELISpot. A significant increase (>20%) of tumor infiltrating CD8+ T cells and effector functions (GZMB+) was observed in the combination-treated cohorts. Additionally, a 5-fold increase in IFNγ producing CD8+ T cells was detected against irradiated KPC cells in combination-treated mice. Altogether, these findings support the potential of VSVd51-LIGHT as a promising immunotherapeutic agent for treating PDAC. Citation Format: Jacob L. Leger, Nawal Amhis, Sarah Mansouri, Maxime Léveillé, Lauren Daniel, Hugo Giguère, Zoé Gerber, Gabriel St-Laurent, Maryline Labrie, Taha Azad, Yves Collin, Lee-Hwa Tai. Oncolytic VSVd51-LIGHT and folfirinox chemotherapy increases anti-tumor immune response in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Mechanisms of Cancer Immunity and Cancer-related Autoimmunity; 2025 Sep 24-27; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(9 Suppl):Abstract nr B003.