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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• 作者：Yunzhou Wu^a ; ¹ ; Jinjiao He^a ; ¹ ; Ying An^a ; Xi Wang^d ; Yunye Liu^a ; Shijun Yan^a ; Xianlong Ye^b ; Jianying Qi^b ; Shenglong Zhu^e ; Qingzhong Yu^c ; Jiechao Yin^a ; Deshan Li^a ; ^{deshangli@163.com" class="auth_mail" title="E-mail the corresponding author} ; Wenfei Wang^a ; ^{wangwenfei@neau.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Newcastle disease virus ; Oncolysis ; Hepatoma ; Hepatocellular carcinoma ; IL-2
• 刊名：Journal of Pharmacological Sciences
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：132
• 期：1
• 页码：24-30
• 全文大小：1015 K

文摘

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.