A novel vaccinia virus enhances anti-tumor efficacy and promotes a long-term anti-tumor response in a murine model of colorectal cancer

被引:20
作者
Wang, Na [1 ]
Wang, Jiwei [1 ]
Zhang, Zhe [1 ]
Cao, Hua [2 ]
Yan, Wenli [1 ]
Chu, Yongchao [1 ]
Dunmall, Louisa S. Chard [3 ]
Wang, Yaohe [1 ,3 ]
机构
[1] Zhengzhou Univ, Acad Med Sci, Sch Basic Med Sci, Natl Ctr Int Res Cell & Gene Therapy, Zhengzhou 450052, Peoples R China
[2] Zhengzhou Univ, Affiliated Hosp 1, ENT Dept, Zhengzhou 450052, Peoples R China
[3] Queen Mary Univ London, Barts Canc Inst, Ctr Biomarkers Biotherapeut, London EC1M 6BQ, England
基金
英国医学研究理事会; 国家重点研发计划;
关键词
ONCOLYTIC VIRAL THERAPY; IL-21; INTERLEUKIN-21; EXPRESSION; GENERATION; VECTORS; SYSTEM;
D O I
10.1016/j.omto.2020.11.002
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 VVL Delta TK Delta N1L 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, VVL Delta TK Delta N1L-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 VVL Delta TK Delta N1L-mIL-21 is a promising therapeutic agent for treatment of CRC.
引用
收藏
页码:71 / 81
页数:11
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