A novel vaccinia virus enhances anti-tumor efficacy and promotes a long-term anti-tumor response in a murine model of colorectal cancer.
A novel vaccinia virus enhances anti-tumor efficacy and promotes a long-term anti-tumor response in a murine model of colorectal cancer.
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一种新型疫苗病毒在小鼠结直肠癌模型中增强了抗肿瘤疗效并促进了长期抗肿瘤反应。
DOI：
10.1016/j.omto.2020.11.002
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发表时间：
2021-03-26
期刊：
影响因子：
--
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Wang N;Wang J;Zhang Z;Cao H;Yan W;Chu Y;Chard Dunmall LS;Wang Y
结直肠癌（CRC）是世界上死亡率和发病率的主要原因之一，并且仍然迫切需要开发持久的疗法来治疗CRC并预防患者的复发。溶瘤病毒疗法（OVT）已经在许多不同的癌症模型中显示出显著的功效。在这里，我们报告了一种新的牛痘病毒（VV）为基础的OVT治疗结直肠癌。新型VV基于最近报道的新型VVLΔTKΔ N1 L病毒，其装备有多效细胞因子白细胞介素-21（IL-21）以增强病毒感染肿瘤细胞后刺激的抗肿瘤免疫应答。与非武装病毒相比，VVLΔTKΔ N1 L-mIL-21在小鼠CMT 93皮下结直肠癌模型中具有上级的体内抗肿瘤功效，主要由CD 8 + T细胞介导。治疗导致针对CMT 93肿瘤细胞的长期免疫力的发展，如通过预防疾病复发所证明的。这些结果表明，VVLΔTKΔ N1 L-mIL-21是一种有前途的治疗CRC的治疗剂。表达IL-21的新型肿瘤靶向复制型牛痘病毒对鼠结肠直肠癌显示出上级抗肿瘤功效，主要由免疫细胞介导。病毒治疗还导致长期肿瘤特异性免疫的发展，以防止复发。这些结果为治疗结肠直肠癌提供了一种有前途的治疗剂。
Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world, and there remains an urgent need to develop long-lasting therapies to treat CRC and prevent recurrence in patients. Oncolytic virus therapy (OVT) has demonstrated remarkable efficacy in a number of different cancer models. Here, we report a novel vaccinia virus (VV)-based OVT for treatment of CRC. The novel VV, based on the recently reported novel VVLΔTKΔN1L virus, was armed with the pleiotropic cytokine interleukin-21 (IL-21) to enhance anti-tumor immune responses stimulated after viral infection of tumor cells. Compared with an unarmed virus, VVLΔTKΔN1L-mIL-21 had a superior anti-tumor efficacy in murine CMT93 subcutaneous CRC models in vivo, mediated mainly by CD8+ T cells. Treatment resulted in development of long-term immunity against CMT93 tumor cells, as evidenced by prevention of disease recurrence. These results demonstrate that VVLΔTKΔN1L-mIL-21 is a promising therapeutic agent for treatment of CRC. A novel tumor-targeted replicating vaccinia virus expressing IL-21 demonstrates a superior antitumor efficacy for murine colorectal cancer, mediated mainly by immune cells. The virus treatment also results in development of long-term tumor-specific immunity to prevent recurrence. These results provide a promising therapeutic agent for treatment of colorectal cancer.
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影响因子：
4.7
作者：
Haddad D
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影响因子：
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作者：
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