title: Genetically engineered Newcastle disease virus expressing interleukin-2 and TNF-related apoptosis-inducing ligand for cancer therapy.
abstract: Recombinant Newcastle disease virus (rNDV) have shown oncolytic therapeutic efficacy in preclinical studies and are currently in clinical trials. In this study, we have evaluated the possibility to enhance the cancer therapeutic potential of NDV by means of inserting both interleukin-2 (IL-2) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) delivered by rNDV. We demonstrated that rNDV expressing TRAIL (rNDV-TRAIL) or both human IL-2 and TRAIL (rNDV-IL-2-TRAIL) significantly enhanced inherent anti-neoplastic of rNDV by inducing apoptosis. And we showed that apoptosis-related genes mRNA expression was increased after treated with rNDV-TRAIL or rNDV-IL-2-TRAIL compared with rNDV and rNDV-IL-2. We also demonstrated that both rNDV-IL-2 and rNDV-IL-2-TRAIL induced proliferation of the CD4(+) and CD8(+) in treated mice and elicited expression of TNF-α and IFN-γ antitumor cytokines. These mice treated with oncolytic agents exhibited significant reduction in tumor development compared with mice treated with the parental virus. In addition, experiments in both hepatocellular carcinoma and melanoma-bearing mice demonstrated that the genetically engineered rNDV-IL-2-TRAIL exhibited prolonged animals' survival compared with rNDV, rNDV-IL-2, and rNDV-TRAIL. In conclusion, the immunotherapy and oncolytic virotherapy properties of NDV can be enhanced by the introduction of IL-2 and TRAIL genes, whose products initiated a broad cascade of immunological affects and induced tumor cells apoptosis in the microenvironment of the immune system.
authors: Biopharmaceutical Teaching and Research Department; College of Life Science; Northeast Agricultural University; Harbin, China.
authors: Fu-Liang
authors: FL
authors: Bai
authors: Biopharmaceutical Teaching and Research Department; College of Life Science; Northeast Agricultural University; Harbin, China.
authors: Yin-Hang
authors: YH
authors: Yu
authors: Biopharmaceutical Teaching and Research Department; College of Life Science; Northeast Agricultural University; Harbin, China.
authors: Hui
authors: H
authors: Tian
authors: Biopharmaceutical Teaching and Research Department; College of Life Science; Northeast Agricultural University; Harbin, China.
authors: Gui-Ping
authors: GP
authors: Ren
authors: Biopharmaceutical Teaching and Research Department; College of Life Science; Northeast Agricultural University; Harbin, China.
authors: Hui
authors: H
authors: Wang
authors: Biopharmaceutical Teaching and Research Department; College of Life Science; Northeast Agricultural University; Harbin, China.
authors: Bing
authors: B
authors: Zhou
authors: Biopharmaceutical Teaching and Research Department; College of Life Science; Northeast Agricultural University; Harbin, China.
authors: Xiao-Hui
authors: XH
authors: Han
authors: USDA-ARS; Southeast Poultry Research Laboratory; Athens, GA USA.
authors: Qing-Zhong
authors: QZ
authors: Yu
authors: Biopharmaceutical Teaching and Research Department; College of Life Science; Northeast Agricultural University; Harbin, China; Biopharmaceutical Teaching and Research Department; College of Life Science; Northeast Agricultural University; Harbin, China.
authors: De-Shan
authors: DS
authors: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy*; D002460:Cell Line; D049109:Cell Proliferation; D002642:Chick Embryo; D005260:Female; D005818:Genetic Engineering; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy*; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009522:Newcastle disease virus / Q000235:genetics* / Q000378:metabolism; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics* / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D007376:Interleukin-2; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: IL-2; TRAIL; cancer therapy; immunotherapy and oncolytic virotherapy; oncolytic agent; rNDV; rNDV-IL-2-TRAIL