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Oncolytic herpes simplex virus type-1 expressing IL-12 efficiently replicates and kills human colorectal cancer cells
Microbial Pathogenesis ( IF 3.3 ) Pub Date : 2021-09-01 , DOI: 10.1016/j.micpath.2021.105164
Nasrin Haghighi-Najafabadi 1 , Farzin Roohvand 2 , Mohammad Sadegh Shams Nosrati 2 , Ladan Teimoori-Toolabi 3 , Kayhan Azadmanesh 2
Affiliation  

An increasing attitude towards oncolytic viruses (OVs) is witnessed following T-VEC's approval. In this study, we aimed to delete ICP47 and insert IL-12 in the ICP34.5 deleted HSV-1 backbone to improve the oncolytic properties and provide an immune-stimulatory effect respectively. The wild-type and recombinant viruses infected both cancerous, SW480 and HCT116, and non-cancerous, HUVEC, cell lines. Green-red Δ47/Δ34.5 was constructed by replacing ICP47 with GFP. Both ICP34.5 copies were replaced by hIL12. Cytotoxicity and growth kinetics of Δ47/Δ34.5/IL12 and Δ47/Δ34.5 were comparable to the wild virus in the cancerous cells. Δ47/Δ34.5/IL12 was able to produce IL12 in the infected cell lines. INF-γ production and PBMC proliferation were observed in the PBMCs treated with the lysate of Δ47/Δ34.5/IL12 infected cells. These results demonstrated that Δ47/Δ34.5/IL12 was competent in taking advantage of the cytotoxic effect of HSV-1 plus immune-stimulatory characteristics of IL-12.



中文翻译:

表达 IL-12 的溶瘤单纯疱疹病毒 1 型有效复制并杀死人类结直肠癌细胞

在 T-VEC 获得批准后,人们对溶瘤病毒 (OV) 的态度与日俱增。在本研究中,我们旨在删除 ICP47 并在 ICP34.5 删除的 HSV-1 骨架中插入 IL-12,以分别改善溶瘤特性并提供免疫刺激作用。野生型和重组病毒感染癌性 SW480 和 HCT116 和非癌性 HUVEC 细胞系。绿色-红色 Δ47/Δ34.5 是通过用 GFP 代替 ICP47 构建的。两个 ICP34.5 拷贝都被 hIL12 取代。Δ47/Δ34.5/IL12和Δ47/Δ34.5的细胞毒性和生长动力学与癌细胞中的野生病毒相当。Δ47/Δ34.5/IL12 能够在受感染的细胞系中产生 IL12。在用Δ47/Δ34.5/IL12感染细胞的裂解物处理的PBMC中观察到INF-γ产生和PBMC增殖。

更新日期:2021-09-10
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