title: Genetically engineered Newcastle disease virus expressing human interferon-λ1 induces apoptosis in gastric adenocarcinoma cells and modulates the Th1/Th2 immune response.
abstract: Interferon-λ1 (IFN-λ1), a recently discovered cytokine of the type III IFN family, was found to be a therapeutic alternative to type I IFN in terms of tumors. Using reverse genetics technique, we generated a recombinant Newcastle disease virus (NDV) LaSota strains named as human IFN‑λ1 recombinant adenovirus (rL-hIFN-λ1) containing human IFN-λ1 gene and further evaluated the expressing of IFN-λ1 in human gastric adenocarcinoma cell line SGC-7901 after infected with rL-hIFN-λ1 by using western blot analysis, RT-PCR and immunofluorescence analyses. IFN-λl specific receptor IFNLR1 was detected on several gastric tumor cell lines including SGC-7901 and AGS and on PBMCs.The expression of the IFN-λ1 proteins reached a high level detected in the supernatant harvested 24 h after the infection of tumor cells. The proliferation changes of SGC infected with rL-hIFN-λ1 was significantly inhibited compared with NDV-infected group. Apoptosis was significantly induced by rL-hIFN-λ1 in gastric cancer cells compared with NDV virus tested by TUNEL assay, western blot analysis and Annexin V flow cytometry. Due to the high dose of IFN-λ1 expressed by the rL-hIFN-λ1-infected tumor cells, the immune study showed that rL-hIFN-λ1 increased IFN-γ production [the T helper cell subtype 1 (Th1) response] and inhibited interleukin (IL)-13 production [the T helper cell subtype 2 (Th2) response] to change the Th1/Th2 response of tumor microenvironment which inhibited tumor growth. This study aims at building recombinant NDV rL-hIFN-λ1 as an efficient antitumor agent.
authors.affiliation: Department of General Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Bu
authors.affiliation: Department of General Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China.
authors.forename: Mi
authors.initials: M
authors.lastname: Li
authors.affiliation: Clinical Medicine College of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China.
authors.forename: Yinghai
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Clinical Medicine College of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China.
authors.forename: Sha
authors.initials: S
authors.lastname: Liu
authors.affiliation: Clinical Medicine College of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China.
authors.forename: Mubin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Jinying
authors.initials: J
authors.lastname: Ge
authors.affiliation: Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Zhigao
authors.initials: Z
authors.lastname: Bu
authors.affiliation: Department of Internal Medicine, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Yan
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005818:Genetic Engineering / Q000379:methods; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics / Q000494:pharmacology*; D009522:Newcastle disease virus / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D000095022:Interferon Lambda
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda