生存素T34A和FilC的异位表达可增强痘苗病毒对小鼠胃癌的溶瘤作用。
The Ectopic Expression of SurvivinT34A and FilC Can Enhance the Oncolytic Effects of Vaccinia Virus in Murine Gastric Cancer.
作者信息
Wang Minglong, Luo Yanxi, Sun Ting, Mao Chenyu, Jiang Yili, Yu Xiongfei, Li Zhongqi, Xie Tian, Wu Fusheng, Yan Hui, Teng Lisong
机构信息
Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou, People's Republic of China.
出版信息
Onco Targets Ther. 2020 Feb 3;13:1011-1025. doi: 10.2147/OTT.S230902. eCollection 2020.
BACKGROUND/AIMS: Anti-tumor vaccines have been shown to be effective in cancer therapeutics ever since the anti-HPV vaccine was developed. Compared to conventional chemotherapy, anti-tumor vaccines can specifically target cancer cells and they have lower side effects. We developed a recombinant vaccinia virus (VACV) (Western Reserve) WR strain, and we tested its anti-tumor effects in an animal model.
METHODS
A recombinant VACV WR strain expressing mutant survivin T34A (SurT34A) and FilC was constructed and validated. Its oncolytic effect was tested in vitro using a CCK-8 assay, and its tolerance and anti-tumor effects were tested in a murine gastric cancer model. The proportion of lymphocytes in the spleen and tumor was determined after antibody-mediated immuno-depletion.
RESULTS
The recombinant VACV showed a stronger replication ability in tumor cells, and it was safe in vivo, even at high doses. The combination of vv-SurT34A and vv-FilC resulted in a stronger anti-tumor effect compared to either construct alone. However, the inhibitory effect of vv-SurT34A was stronger than the combination. The recombinant VACV activated the host immune response, as indicated by lymphocyte infiltration in the spleen and tumor tissues.
CONCLUSION
The recombinant VACV WR strain expressing SurT34A and FilC is a safe and effective anti-tumor vaccine.
背景/目的：自从抗人乳头瘤病毒（HPV）疫苗研发出来后，抗肿瘤疫苗已被证明在癌症治疗中有效。与传统化疗相比，抗肿瘤疫苗能够特异性地靶向癌细胞，且副作用更小。我们研发了一种重组痘苗病毒（VACV）（西储株）WR株，并在动物模型中测试了其抗肿瘤效果。
方法
构建并验证了一种表达突变型生存素T34A（SurT34A）和FilC的重组VACV WR株。使用CCK-8测定法在体外测试其溶瘤效果，并在小鼠胃癌模型中测试其耐受性和抗肿瘤效果。在抗体介导的免疫耗竭后，测定脾脏和肿瘤中淋巴细胞的比例。
结果
重组VACV在肿瘤细胞中显示出更强的复制能力，并且即使在高剂量下在体内也是安全的。与单独的任何一种构建体相比，vv-SurT34A和vv-FilC的组合产生了更强的抗肿瘤效果。然而，vv-SurT34A的抑制作用比该组合更强。如脾脏和肿瘤组织中的淋巴细胞浸润所示，重组VACV激活了宿主免疫反应。
结论
表达SurT34A和FilC的重组VACV WR株是一种安全有效的抗肿瘤疫苗。
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