%0 Journal Article %T Oncolytic vaccinia virus harboring CLEC2A gene enhances viral replication and antitumor efficacy. %A Gao C %A Ying Q %A Qiu Y %A Ren N %A Chen K %A Zhou Y %A Ye T %A Li G %J Mol Ther Oncol %V 32 %N 3 %D 2024 Sep 19 %M 39006946 暂无%R 10.1016/j.omton.2024.200823 %X In the field of innovative cancer treatment strategies, oncolytic vaccinia virus (VV)es have gained traction as promising vectors. In the current study, we inserted the human C-type lectin domain family 2 member A (CLEC2A) gene into VV, creating a replicating therapeutic, oncoVV-CLEC2A. The findings reveal that oncoVV-CLEC2A effectively suppresses colorectal proliferation of mouse xenografts and a range of human cancer cell lines by augmenting viral reproduction capabilities, including the lung cancer H460 cell line, colorectal cancer cell lines (HCT116 and SW620), and hepatocellular carcinoma HuH-7 cell line. Moreover, it is evident that oncoVV-CLEC2A can induce antitumor immunity by boosting cytokine production but not antivirus response, and enhancing calreticulin expression. Further investigation indicates that oncoVV-CLEC2A can enhance antitumor capabilities by activating natural killer cells to produce interferon-γ and induce M1-like macrophage polarization. These findings shed light on the antitumor mechanisms of oncoVV-CLEC2A, provide a theoretical basis for oncolytic therapies, and lay the groundwork for novel strategies for modifying VVs.