表达 IL-12 的溶瘤单纯疱疹病毒 1 能够高效复制并杀伤人类结直肠癌细胞。
Oncolytic herpes simplex virus type-1 expressing IL-12 efficiently replicates and kills human colorectal cancer cells.
机构信息
Virology Department, Pasteur Institute of Iran, Iran; Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Iran.
Virology Department, Pasteur Institute of Iran, Iran.
出版信息
Microb Pathog. 2021 Nov;160:105164. doi: 10.1016/j.micpath.2021.105164. Epub 2021 Sep 1.
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.
在 T-VEC 获得批准后，人们对溶瘤病毒（OVs）的态度越来越积极。在这项研究中，我们旨在删除 ICP47 并在 ICP34.5 缺失的 HSV-1 骨架中插入 IL-12，分别提高溶瘤特性和提供免疫刺激作用。野生型和重组病毒感染了癌细胞 SW480 和 HCT116 以及非癌细胞 HUVEC 细胞系。通过用 GFP 替换 ICP47 构建了绿色-红色 Δ47/Δ34.5。两个 ICP34.5 拷贝均被 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 能够在感染的细胞系中产生 IL12。在用感染了 Δ47/Δ34.5/IL12 的细胞的裂解物处理的 PBMC 中观察到 INF-γ 产生和 PBMC 增殖。这些结果表明，Δ47/Δ34.5/IL12 能够利用 HSV-1 的细胞毒性作用和 IL-12 的免疫刺激特性。
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