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Recombinant Newcastle disease virus (NDV/Anh-IL-2) expressing human IL-2 as a potential candidate for suppresses growth of hepatoma therapy

Author:
Wu, Yunzhou, He, Jinjiao, An, Ying, Wang, Xi, Liu, Yunye, Yan, Shijun, Ye, Xianlong, Qi, Jianying, Zhu, Shenglong, Yu, Qingzhong, Yin, Jiechao, Li, Deshan, Wang, Wenfei
Source:
Journal of Pharmacological Sciences 2016 v.132 no.1 pp. 24-30
ISSN:
1347-8613
Subject:
Newcastle disease virus, antineoplastic activity, clinical trials, hepatoma, humans, immune response, immunologic memory, immunostimulants, immunostimulation (physiological), in vivo studies, interleukin-2, laboratory animals, lymphocytes, mice, microbial growth, neoplasm cells, therapeutics, vaccines, viruses
Abstract:
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.
Handle:
10113/5509862