PDF(Pubmed)
Abstract：
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.
摘要：
在创新癌症治疗策略领域，溶瘤痘苗病毒（VV）已成为有前途的载体。在目前的研究中,我们将人C型凝集素结构域家族2成员A（CLEC2A）基因插入VV，创造一种复制的治疗剂，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肠直肠增殖，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的产生而不是抗病毒反应来诱导抗肿瘤免疫，增强钙网蛋白表达。进一步的研究表明，癌VV-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。这些发现揭示了癌VV-CLEC2A的抗肿瘤机制，为溶瘤治疗提供理论依据，并为修改VV的新策略奠定基础。
