PDF(Pubmed)
Abstract：
Hepatocellular carcinoma is a refractory tumor with poor prognosis and high mortality. Many oncolytic viruses are currently being investigated for the treatment of hepatocellular carcinoma. Based on previous studies, we constructed a recombinant GM-CSF-carrying Sindbis virus, named SINV-GM-CSF, which contains a mutation (G to S) at amino acid 285 in the nsp1 protein of the viral vector. The potential of this mutated vector for liver cancer therapy was verified at the cellular level and in vivo, respectively, and the changes in the tumor microenvironment after treatment were also described. The results showed that the Sindbis virus could effectively infect hepatocellular carcinoma cell lines and induce cell death. Furthermore, the addition of GM-CSF enhanced the tumor-killing effect of the Sindbis virus and increased the number of immune cells in the intra-tumor microenvironment during the treatment. In particular, SINV-GM-CSF was able to efficiently kill tumors in a mouse tumor model of hepatocellular carcinoma by regulating the elevation of M1-type macrophages (which have a tumor-resistant ability) and the decrease in M2-type macrophages (which have a tumor-promoting capacity). Overall, SINV-GM-CSF is an attractive vector platform with clinical potential for use as a safe and effective oncolytic virus.
摘要：
肝细胞癌是一种难治性肿瘤，预后差，死亡率高。目前正在研究许多溶瘤病毒用于治疗肝细胞癌。根据以前的研究，我们构建了携带GM-CSF的辛德毕斯病毒，命名为SINV-GM-CSF，其在病毒载体的nsp1蛋白的氨基酸285处含有突变(G到S)。在细胞水平和体内验证了这种突变载体用于肝癌治疗的潜力，分别,并描述了治疗后肿瘤微环境的变化。结果表明，辛德毕斯病毒能有效感染肝癌细胞系并诱导细胞死亡。此外，GM-CSF的加入增强了辛德毕斯病毒的肿瘤杀伤作用,并增加了治疗期间肿瘤内微环境中免疫细胞的数量.特别是,在肝细胞癌的小鼠肿瘤模型中,SINV-GM-CSF能够通过调节M1型巨噬细胞(其具有肿瘤抗性能力)的升高和M2型巨噬细胞(其具有肿瘤促进能力)的减少而有效地杀死肿瘤。总的来说,SINV-GM-CSF是一种有吸引力的载体平台，具有作为安全有效的溶瘤病毒的临床潜力。
