Oncolytic vaccinia virus expressing non-secreted decoy-resistant IL-18 mutein elicits potent antitumor effects with enhanced safety

T cells, thereby transforming immunologically "cold" tumors into "hot" tumors. However, nsmDR-18-expressing oVV treatment also elevated regulatory T cells (Tregs) and upregulated immune checkpoint molecules (PD-1, PD-L1, and CTLA-4). Combining nsmDR-18-expressing oVV with anti-CTLA-4 antibody significantly improved overall survival and induced systemic, tumor-specific antitumor immunity. These results highlight the potential of nsmDR-18-expressing oVV as a therapeutic strategy, supporting further exploration in clinical trials.