Oncolytic vaccinia virus harboring CLEC2A gene enhances viral replication and antitumor efficacy

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 oncoVVCLEC2A can enhance antitumor capabilities by activating natural killer cells to produce interferon-g 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.