文章：

仙台病毒融合基因的肿瘤免疫治疗

Cancer immunotherapy using the Fusion gene of Sendai virus 

原文发布日期：2019-08-06 

英文摘要：

Inactivated Sendai virus particle (or hemagglutinating virus of Japan envelope; HVJ-E) has been previously reported to possess antitumour properties that activate antitumour immunity. Two glycoproteins, fusion (F) and hemagglutinin-neuraminidase (HN), are present on the surface of HVJ-E. HN is necessary for binding to receptors such as acidic gangliosides, and F induces membrane fusion by associating with membrane lipids. We previously reported that liposomes reconstituted with F but not HN showed antitumour activity by inducing IL-6 secretion in dendritic cells (DCs), suggesting that F protein is capable of eliciting antitumour activity. Here, we attempted to deliver F gene into tumour tissue in mice by electroporation and demonstrated that F gene therapy retarded tumour growth, increased CD4+ and CD8+ T-cell infiltration into tumours and induced tumour-specific IFN-γ T-cell response. However, neutralisation of IL-6R signalling did not impact F plasmid-mediated antitumour effect. Instead, we found that F plasmid treatment resulted in a significant increase in the secretion of the chemokine RANTES (regulated upon activation, normal T cell expressed and secreted) by tumour-infiltrating T cells. Neutralising antibody against RANTES abolished the antitumour effect of F plasmid treatment in a dose-dependent manner. Thus, F gene therapy may show promise as a novel therapeutic for single or combined cancer immunotherapy. 

摘要翻译： 

既往研究表明，灭活仙台病毒颗粒（又称日本血凝病毒包膜；HVJ-E）具有激活抗肿瘤免疫的特性。HVJ-E表面存在两种糖蛋白：融合蛋白（F）和血凝素-神经氨酸酶（HN）。HN是结合酸性神经节苷脂等受体所必需的组分，而F蛋白通过与膜脂质结合诱导膜融合。我们前期研究发现，仅重构F蛋白（不含HN）的脂质体可通过诱导树突状细胞（DCs）分泌IL-6发挥抗肿瘤活性，提示F蛋白具备激发抗肿瘤效应的能力。本研究尝试通过电穿孔方式将F基因递送至小鼠肿瘤组织，证实F基因治疗可延缓肿瘤生长、增加CD4+和CD8+ T细胞在肿瘤中的浸润，并诱导肿瘤特异性IFN-γ T细胞应答。然而，IL-6R信号通路中和并未影响F质粒介导的抗肿瘤效应。进一步研究发现，F质粒处理可显著增加肿瘤浸润T细胞分泌趋化因子RANTES（活化调节趋化因子）。使用RANTES中和抗体能以剂量依赖性方式完全消除F质粒治疗的抗肿瘤效果。因此，F基因疗法有望成为单一或联合癌症免疫治疗的新型策略。

原文链接：

Cancer immunotherapy using the Fusion gene of Sendai virus