Wang Na, Wang Jiwei, Zhang Zhe, Cao Hua, Yan Wenli, Chu Yongchao, Chard Dunmall Louisa S, Wang Yaohe
National Centre for International Research in Cell and Gene Therapy, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China.
ENT Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, China.
Mol Ther Oncolytics. 2020 Nov 17;20:71-81. doi: 10.1016/j.omto.2020.11.002. eCollection 2021 Mar 26.
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 , 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.
结直肠癌（CRC）是全球主要的致死和致病原因之一，因此迫切需要开发长效疗法来治疗CRC并预防患者复发。溶瘤病毒疗法（OVT）在许多不同的癌症模型中都显示出显著疗效。在此，我们报告一种基于新型痘苗病毒（VV）的OVT用于治疗CRC。这种新型VV基于最近报道的新型VVLΔTKΔN1L病毒构建，携有多效性细胞因子白细胞介素-21（IL-21），以增强肿瘤细胞被病毒感染后刺激产生的抗肿瘤免疫反应。与无武装的病毒相比，VVLΔTKΔN1L-mIL-21在小鼠CMT93皮下CRC模型中具有更强的抗肿瘤疗效，主要由CD8 T细胞介导。治疗导致对CMT93肿瘤细胞产生长期免疫力，疾病复发得到预防就是证据。这些结果表明，VVLΔTKΔN1L-mIL-21是一种有前景的治疗CRC的药物。
