In situ blockade of TNF-TNFR2 axis via oncolytic adenovirus improves antitumor efficacy in solid tumors.

ABSTRACT: Tumor necrosis factor (TNF) has been recognized as an immune activation factor in tumor immunotherapy. Our study demonstrated that TNF blockade markedly enhanced the antitumor efficacy of oncolytic adenovirus (AdV) therapy. To minimize systemic side effects, we engineered a recombinant oncolytic AdV encoding a TNF inhibitor (AdV-TNFi) to confine TNF blockade within the tumor microenvironment (TME). AdV-TNFi significantly improved therapeutic outcomes across various solid tumor models, including four murine and two golden hamster cancers. Immune cell profiling identified CD8⁺ T cells as the primary mediators of AdV-TNFi-induced antitumor effects, rather than CD4⁺ T or NK cells. Additionally, AdV-TNFi significantly decreased the infiltration of suppressive myeloid-deriv

SUBMITTER: Kang X 

PROVIDER: S-EPMC11853363 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature