title: Recombinant Newcastle Disease virus Expressing IL15 Demonstrates Promising Antitumor Efficiency in Melanoma Model.
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 intra-tumoral (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-γ 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 melanoma.
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang District, Harbin, China.
authors.forename: Zeshan
authors.initials: Z
authors.lastname: Niu
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang District, Harbin, China.
authors.forename: Fuliang
authors.initials: F
authors.lastname: Bai
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang District, Harbin, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Sun
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang District, Harbin, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang District, Harbin, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yu
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang District, Harbin, China.
authors.forename: Jiechao
authors.initials: J
authors.lastname: Yin
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang District, Harbin, China.
authors.forename: Siming
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Life Sciences, University of Chinese Academy of Sciences, Yuquan Road 19, Shi Jingshan District, Beijing, China.
authors.forename: Tianhe
authors.initials: T
authors.lastname: Li
authors.affiliation: College of Biological Science and Technology, Heilongjiang Bayi Agricultural University, Xinfeng Road 2, Hi-tech District, Daqing, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Cao
authors.affiliation: Southeast Poultry Research Laboratory, Agricultural Research Service, United States Department of Agriculture, 934 College Station Road, Athens, GA 30605, USA.
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Southeast Poultry Research Laboratory, Agricultural Research Service, United States Department of Agriculture, 934 College Station Road, Athens, GA 30605, USA.
authors.forename: Yunzhou
authors.initials: Y
authors.lastname: Wu
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang District, Harbin, China.
authors.forename: Guiping
authors.initials: G
authors.lastname: Ren
authors.affiliation: College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang District, Harbin, China deshanli@163.com.
authors.forename: Deshan
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002642:Chick Embryo; D006224:Cricetinae; D056945:Hep G2 Cells; D006801:Humans; D019409:Interleukin-15 / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000235:genetics / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D008545:Melanoma / Q000401:mortality / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009522:Newcastle disease virus / Q000235:genetics* / Q000378:metabolism; D050130:Oncolytic Virotherapy / Q000379:methods*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: C569274:IL15 protein, human; C508594:IL2 protein, human; D019409:Interleukin-15; D007376:Interleukin-2
keywords: IL15; IL2; Melanoma; Safer; Tumor agent.; rNDV