title: Genetically engineered Newcastle disease virus expressing interleukin 2 is a potential drug candidate for cancer immunotherapy.
abstract: Newcastle disease virus (NDV) is an intrinsically tumor-specific virus, several clinical trials have reported that mesogenic NDV is a safe and effective agent for human cancer therapy. Interleukin 2 (IL2) is a cytokine that stimulates T cell propagation to trigger innate and adaptive immunity. IL2 has been used for cancer therapy and has achieved curative effects. In this study, a recombinant NDV LaSota strain expressing human interleukin 2 (rLaSota/IL2) was generated. The ability of rLaSota/IL2 to express human IL2 was detected in the infected tumor cells. In addition, the activity of IL2 was analyzed. The antitumor potential of rLaSota/IL2 was studied by xenograph mice carrying H22 and B16-F10 cells. Tumor-specific CD4(+) and CD8(+) T cells and MHC II were also analyzed in the two tumor-bearing models. Our study showed that rLaSota/IL2 significantly stimulated tumor-specific cytotoxic T-lymphocyte (CTL) responses and increased regulatory CD4(+) and cytotoxic CD8(+) T cells proliferation. The treatment with rLaSota/IL2 led to tumor regression in tumor-bearing mice and prolonged the survival of tumor-bearing mice. Furthermore, tumor challenging experiments demonstrated that rLaSota/IL2 invoked mice a unique capacity to remember a pathogen through the generation of memory T cells, which protect the host in the event of reinfection and form adaptive immune system. The result indicates that tumor-infiltrating CD4(+) T regulatory cells may denote the effective regression of tumors. Taken together, rLaSota/IL2 has potential for immunotherapy and oncolytic therapy of cancers and may be an ideal candidate for clinical application in future cancer therapy.
authors.affiliation: Biopharmaceutical Teaching and Research Section, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Fuliang
authors.initials: F
authors.lastname: Bai
authors.affiliation: Biopharmaceutical Teaching and Research Section, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Zeshan
authors.initials: Z
authors.lastname: Niu
authors.affiliation: Biopharmaceutical Teaching and Research Section, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
authors.affiliation: Biopharmaceutical Teaching and Research Section, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Siming
authors.initials: S
authors.lastname: Li
authors.affiliation: Biopharmaceutical Teaching and Research Section, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Biopharmaceutical Teaching and Research Section, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Tianyuan
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Biopharmaceutical Teaching and Research Section, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Guiping
authors.initials: G
authors.lastname: Ren
authors.affiliation: Biopharmaceutical Teaching and Research Section, College of Life Science, Northeast Agricultural University, Harbin 150030, China. Electronic address: desganli@163.com.
authors.forename: Deshan
authors.initials: D
authors.lastname: Li
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015870:Gene Expression; D005818:Genetic Engineering; D006801:Humans; D007156:Immunologic Memory; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008546:Melanoma, Experimental / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D051379:Mice; D009522:Newcastle disease virus / Q000235:genetics*; D050130:Oncolytic Virotherapy / Q000379:methods; D012878:Skin Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D047368:Tumor Burden
chemical_list: D007376:Interleukin-2
keywords: Cancer therapy; IL2; Immunotherapy; NDV; Oncolytic therapy; rLaSota/IL2