Work

AVL-armed oncolytic vaccinia virus promotes viral replication and boosts antitumor immunity via increasing ROS levels in pancreatic cancer

Year: 2024

Type: article

Abstract: lectin-armed oncolytic vaccinia virus (oncoVV-AVL) on PC, AsPC-1 and PANC-1 cells underwent treatment with oncoVV-AVL. Our findings revealed that oncoVV-AVL possesses the capacity to heighten oncolytic effects on PC cells and incite the production of diverse cytokines like tumor necrosis factor-α, interleukin-6 (IL-6), IL-8, and interferon-I (IFN-I), without triggering antiviral responses. Additionally, oncoVV-AVL can significantly elevate the levels of ROS in PC cells, initiating an oxidative stress response that promotes viral replication, apoptosis, and autophagy. Moreover, in xenograft tumor models, oncoVV-AVL notably restrained PC growth, enhanced IFN-γ levels in the bloodstream, and reprogrammed macrophages. Our investigation indicates that oncoVV-AVL boosts the efficacy of antitumor actions against PC tumors by orchestrating reactive oxygen species-triggered viral replication, fostering M1 polarization, and reshaping the tumor microenvironment to transform cold PC tumors into hot ones. These findings imply that oncoVV-AVL could present a novel therapeutic approach for treating PC tumors.

Source: Molecular Therapy Oncology

DOI: 10.1016/j.omton.2024.200878