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

Authors: WU, YUNZHOU - Northeast Agricultural University, China; HE, JINJIAO - Northeast Agricultural University, China; AN, YING - Northeast Agricultural University, China; WANG, XI - Harbin Medical University; LIU, YUNYE - Northeast Agricultural University, China; YAN, SHIJUN - Northeast Agricultural University, China; YE, XIANLONG - Henan Normal University; QI, JIANYING - Henan Normal University; ZHU, SHENGLONG - Jiangnan University; Yu, Qingzhong; YIN, JIECHAO - Northeast Agricultural University, China; LI, DESHAN - Northeast Agricultural University, China; WANG, WENFEI - Northeast Agricultural University, China

Submitted to: Journal of Pharmacological Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/24/2016
Publication Date: 4/27/2016
Publication URL: http://handle.nal.usda.gov/10113/5509862
Citation: Wu, Y., He, J., An, Y., Wang, X., Liu, Y., Yan, S., Ye, X., Qi, J., Zhu, S., Yu, Q., Yin, J., Li, D., Wang, W. 2016. Recombinant Newcastle disease virus (NDV/Anh-IL-2) expressing human IL-2 as a potential candidate for suppresses growth of hepatoma therapy. Journal of Pharmacological Sciences. 132(1):24-30. doi:10.1016/j.jphs.2016.03.012.

Interpretive Summary: Newcastle disease virus (NDV) is an avian pathogen and does not readily grow in human. However, some strains of NDV can selectively grow in human tumor cells and have been used for anticancer therapy in preclinical studies. Previous studies have shown that human Interleukin-2 (IL-2), a cytokine, can inhibit tumor growth by activating innate immunity. In the present study we synchronized the power of the NDV and the cytokine in anticancer therapy. NDV Anhinga strain was used as a backbone to construct a recombinant virus (NDV/Anh-IL-2) expressing IL-2. Mice with liver tumor were used a cancer model and treated with NDV/Anh-IL-2. The results showed that the NDV/Anh-IL-2 could express soluble IL-2 and effectively inhibit the growth of liver tumor in mice. After 60 days treatment mice were completely cured for the liver cancer and were well protected when re-challenged with the same tumor cell. The data suggest that the recombinant NDV/Anh-IL-2 virus is a promising candidate for anticancer therapy.

Technical 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 posttreatment, 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.