研究概要
在创新性癌症治疗策略领域,溶瘤痘苗病毒(VV)作为有前景的载体已日益受到关注。
中文摘要
在创新性癌症治疗策略领域,溶瘤痘苗病毒(VV)作为有前景的载体已受到越来越多的关注。在本研究中,我们将人类C型凝集素结构域家族2成员A(CLEC2A)基因插入VV中,构建了复制型治疗剂oncoVV-CLEC2A。研究结果表明,oncoVV-CLEC2A通过增强病毒复制能力,有效抑制了小鼠异种移植瘤及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)以及肝细胞癌HuH-7细胞系。此外,研究还表明,oncoVV-CLEC2A能够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可通过激活NK 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,为溶瘤治疗提供了理论基础,并为改造VV的新策略奠定了基础。
展开英文摘要原文
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.
论文信息
- 作者
- Gao C、Ying Q、Qiu Y、Ren N、Chen K、Zhou Y、Ye T、Li G
- 单位
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.China
- 期刊
- Molecular therapy. Oncology2024 Sep 19