Intravenous Injections of a Rationally Selected Oncolytic Herpes Virus as a Potent Virotherapy for Hepatocellular Carcinoma
Intravenous Injections of a Rationally Selected Oncolytic Herpes Virus as a Potent Virotherapy for Hepatocellular Carcinoma
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静脉注射合理选择的溶瘤疱疹病毒作为肝细胞癌的有效病毒疗法。
DOI：
10.1016/j.omto.2019.09.004
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发表时间：
2019-12-20
期刊：
影响因子：
--
通讯作者：
Xia, Ningshao
中科院分区：
文献类型：
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作者：
Luo, Yong;Lin, Chaolong;Xia, Ningshao
肝细胞癌（HCC）作为一种迫切需要新治疗方案的临床环境，显示出溶瘤病毒治疗的诱人机会。在这里，我们报告了一种新的基于单纯疱疹病毒1型（HSV-1）的靶向肝癌的溶瘤载体，命名为Ld 0-GFP，它来自溶瘤ICP 0-null病毒（d 0-GFP），具有融合表型，是一种新的针对肝癌和其他类型的癌细胞的杀伤细胞。与d 0-GFP相比，Ld 0-GFP在体外和体内均表现出上级的癌细胞杀伤能力。Ld 0-GFP靶向广谱HCC细胞，并可导致显著增强的免疫原性肿瘤细胞死亡。瘤内和静脉注射Ld 0-GFP在多种肿瘤模型中显示出有效的抗肿瘤能力，导致存活率增加。我们推测，溶瘤病毒更活跃的细胞杀伤能力和增强的免疫原性细胞死亡可能导致更好的肿瘤消退。此外，Ld 0-GFP具有改善的安全性，显示出降低的神经毒力和全身毒性。Ld 0-GFP病毒疗法可能为HCC的局部和全身治疗提供潜在的毒性更小，更有效的选择。这种方法还为正在进行的开发用于癌症治疗的最佳溶瘤载体的努力提供了新的见解。
As a clinical setting in which novel treatment options are urgently needed, hepatocellular carcinoma (HCC) exhibits intriguing opportunities for oncolytic virotherapy. Here we report the rational generation of a novel herpes simplex virus type 1 (HSV-1)-based oncolytic vector for targeting HCC, named Ld0-GFP, which was derived from oncolytic ICP0-null virus (d0-GFP), had a fusogenic phenotype, and was a novel killer against HCC as well as other types of cancer cells. Compared with d0-GFP, Ld0-GFP exhibited superior cancer cell-killing ability in vitro and in vivo. Ld0-GFP targets a broad spectrum of HCC cells and can result in significantly enhanced immunogenic tumor cell death. Intratumoral and intravenous injections of Ld0-GFP showed effective antitumor capabilities in multiple tumor models, leading to increased survival. We speculated that more active cell-killing capability of oncolytic virus and enhanced immunogenic cell death may lead to better tumor regression. Additionally, Ld0-GFP had an improved safety profile, showing reduced neurovirulence and systemic toxicity. Ld0-GFP virotherapy could offer a potentially less toxic, more effective option for both local and systemic treatment of HCC. This approach also provides novel insights toward ongoing efforts to develop an optimal oncolytic vector for cancer therapy.