|NIU, ZESHAN - Northwest Agricultural University|
|BAI, FULIANG - Northeast Agricultural University|
|SUN, TIAN - Northeast Agricultural University|
|TIAN, HUI - Northeast Agricultural University|
|YU, DAN - Northeast Agricultural University|
|YIN, JIECHAO - Northeast Agricultural University|
|LI, SIMING - Northeast Agricultural University|
|LI, TIANHE - Northeast Agricultural University|
|CAO, HONGWEI - Heilongjiang Bayi Agricultural University (HLAU)|
|WU, YUNZHOU - Northeast Agricultural University|
|REN, GUIPING - Northeast Agricultural University|
|LI, DESHAN - Northeast Agricultural University|
Submitted to: Technology in Cancer Research and Treatment
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/1/2014
Publication Date: 9/1/2014
Publication URL: http://handle.nal.usda.gov/10113/60139
Citation: Niu, Z., Bai, F., Sun, T., Tian, H., Yu, D., Yin, J., Li, S., Li, T., Cao, H., Yu, Q., Wu, Y., Ren, G., Li, D. 2014. Recombinant Newcastle disease virus expressing IL15 demonstrates promising antitumor efficiency in melanoma model. Technology in Cancer Research and Treatment. DOI: 10.7785/tcrt.2012.500414.
Interpretive Summary: Newcastle Disease Virus (NDV), an avian pathogen, can selectively grow in human tumor cells, and has been used for anticancer therapy in preclinical studies. Previous studies have shown that Interleukin 2 (IL-2) and Interleukin 15 (IL-15) can inhibit tumor growth by activating innate immunity. In the present study we synchronized the power of the NDV and the cytokines in anticancer therapy. Two recombinant NDV viruses carrying the IL2 or IL5 gene, respectively, were generated for anticancer research. These two recombinant viruses replicated efficiently in tumor cell lines and expressed IL15 or IL2 proteins. Treatment of melanoma tumor-bearing mice with the recombinant viruses suppressed tumor growth and increased survival rate compared to the non-treated control mice. The results of this study suggest that NDV recombinant viruses expressing the IL2 and IL5 are potent candidates for anti-skin cancer therapy.
Technical Abstract: Recombinant Newcastle Disease Virus (rNDV) has shown oncolytic therapeutic effect in preclinical studies. Previous data indicate that rNDV carrying IL2 has shown promise in cancer therapy. Due to the significant side effects of IL2, IL15 has been introduced into cancer therapy. A number of studies have suggested that IL15 efficiently enhances the activities of CTL and NK cells and inhibits the tumor recurrence and metastasis. Furthermore, IL15 is less toxic than IL2. Therefore, we hypothesize that a recombinant NDV expressing IL15 would be a promising agent for the treatment of malignant tumors. The human IL15 gene or IL2 gene was incorporated into the genome of lentogenic LaSota strain at the position between the HN and L genes (namely rNDV-IL15 or rNDV-IL2). The two viruses efficiently infected tumor cells and expressed IL15 or IL2 protein. Melanoma tumor-bearing mice were treated by intratumoral (i.t.) injection of rNDV-IL15 or rNDV-IL2. Both rNDV-IL15 and rNDV-IL2 effectively suppressed tumor growth compared with rNDV. The 120-day survival rate of rNDV-IL15-treated group was 12.5% higher than that of rNDV-IL2 group, although the difference was not statistically significant, both recombinant viruses had strong abilities to induce CD41 T cell and CTL cell responses. However, rNDV-IL15 significantly induced more IFN-' release and stimulated more CD81 T cells infiltration in the tumor sites compared with rNDV-IL2. In the tumor re-challenged experiment, the survival rates of rNDV-IL15 group and rNDV-IL2 group were statistically higher than that of PBS group. The survival rate of rNDV-IL15 group was 26.67% higher than that of rNDV-IL2 group although the difference was not statistically significant. In conclusion, rNDV-IL15 is a promising antitumor agent against elanoma.