Recombinant Newcastle disease virus (NDV/Anh-IL-2) expressing human IL-2 as a potential candidate for suppresses growth of hepatoma therapy
Recombinant Newcastle disease virus (NDV/Anh-IL-2) expressing human IL-2 as a potential candidate for suppresses growth of hepatoma therapy
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表达人 IL-2 的重组新城疫病毒 (NDV/Anh-IL-2) 作为抑制肝癌生长的潜在候选药物
DOI：
10.1016/j.jphs.2016.03.012
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发表时间：
2016-09-01
影响因子：
3.5
通讯作者：
Wang, Wenfei
中科院分区：
文献类型：
--
作者：
Wu, Yunzhou;He, Jinjiao;Wang, Wenfei
新城疫病毒（NDV）已在临床前研究中显示出溶瘤治疗效果，目前已被批准进行临床试验。NDV Anhinga菌株是一种中源菌株，应归为溶菌菌株，在肝细胞癌中具有治疗作用。在本研究中，我们评估了NDV Anhinga株在体内引发免疫反应的能力，以及作为表达肿瘤治疗因子的疫苗载体的可能性。白细胞介素-2 （IL-2）可以增强对肿瘤细胞的免疫反应。因此，我们以NDV Anhinga株为骨架构建了表达IL-2的重组病毒（NDV/Anh-IL-2）。病毒生长曲线显示，与野生型相比，重组NDV/Anh-IL-2的产生略有延迟。NDV/Anh-IL-2菌株能在体内表达可溶性IL-2，有效抑制肝癌细胞的生长。治疗后60天，经前一次治疗完全治愈的小鼠，再用相同的肿瘤细胞攻击时，具有良好的保护作用。h&e染色切片显示，NDV/Anh-IL-2处理组淋巴细胞明显浸润。NDV Anhinga毒株不仅能直接杀伤肿瘤，而且在体内杀伤肿瘤时还能引起免疫反应和强烈的免疫记忆。综上所述，Anhinga菌株可作为肿瘤治疗的有效载体；表达可溶性IL-2的重组NDV/Anh-IL-2菌株是肝癌治疗的有希望的候选菌株。(C) 2016年作者。由Elsevier B.V.代表日本药理学会制作和主办。这是一篇基于CC BY-NC-ND许可的开放获取文章
Newcastle disease virus (NDV) have shown oncolytic therapeutic efficacy in preclinical study and are currently approved for clinical trials. NDV Anhinga strain which is a mesogenic strain should be classified as lytic strain and has a therapeutic efficacy in hepatocellular cancer. In this study, we evaluated the capacity of NDV Anhinga strain to elicit immune reaction in vivo and the possibility for using as a vaccine vector for expressing tumor therapeutic factors. Interleukin-2 (IL-2) could boost the immune response against the tumor cells. Therefore, we use NDV Anhinga strain as backbone to construct a recombinant virus (NDV/Anh-IL-2) expressing IL-2. The virus growth curve showed that the production of recombinant NDV/Anh-IL-2 was slightly delayed compared to the wild type. The NDV/Anh-IL-2 strain could express soluble IL-2 and effectively inhibit the growth of hepatocellular carcinoma in vivo. 60 days post-treatment, mice which were completely cured by previous treatment were well protected when rechallenged with the same tumor cell. From the H&E-stained sections, intense infiltration of lymphocyte was observed in the NDV Anhinga strain treated group, especially in NDV/Anh-IL-2 group. The NDV Anhinga strain could not only kill the tumor directly, but could also elicit immune reaction and a potent immunological memory when killing tumor in vivo. In conclusion, the Anhinga strain could be an effective vector for tumor therapy; the recombinant NDV/Anh-IL-2 strain expressing soluble IL-2 is a promising candidate for hepatoma therapy. (C) 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license