在创新癌症治疗策略领域，溶瘤痘苗病毒 (VV) 作为有前途的载体而受到关注。在当前的研究中，我们将人 C 型凝集素结构域家族 2 成员 A (CLEC2A) 基因插入 VV，创建了一种复制治疗剂 oncoVV-CLEC2A。研究结果表明，oncoVV-CLEC2A 通过增强病毒繁殖能力，有效抑制小鼠异种移植物和一系列人类癌细胞系的结直肠增殖，包括肺癌 H460 细胞系、结直肠癌细胞系（HCT116 和 SW620）和肝细胞癌 HuH -7细胞系。此外，很明显，oncoVV-CLEC2A 可以通过促进细胞因子产生而非抗病毒反应以及增强钙网蛋白表达来诱导抗肿瘤免疫。进一步研究表明oncoVV-CLEC2A可以通过激活自然杀伤细胞产生干扰素-γ并诱导M1样巨噬细胞极化来增强抗肿瘤能力。这些发现揭示了 oncoVV-CLEC2A 的抗肿瘤机制，为溶瘤疗法提供了理论基础，并为修改 VV 的新策略奠定了基础。© 2024 作者。

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.© 2024 The Author(s).