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

• Published in: Molecular Therapy: Oncology 2024-09, Vol.32 (3), p.200823, Article 200823
• Main Authors: Gao, Chunqing, Ying, Qi, Qiu, Yufeng, Ren, Ningbo, Chen, Kan, Zhou, Yanrong, Ye, Ting, Li, Gongchu
• Format: Article
• Language: English
• Subjects: antitumor; C-type lectin domain family 2 member A; MT: Regular Issue; NK cells; oncolytic vaccinia virus; viral replication
• ISSN: 2950-3299; 2950-3299
• DOI: 10.1016/j.omton.2024.200823

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 ( ) 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.