title: Antitumor effects obtained by autologous Lewis lung cancer cell vaccine engineered to secrete mouse interleukin 27 by means of cationic liposome.
abstract: Interleukin-27 (IL-27), a novel IL-6/IL-12 family cytokine, plays an important role in the early regulation of Th1 responses. The cytokine IL-27 can exert a variety of immune-regulatory functions including cytotoxic T lymphocyte (CTL), CD4+, CD8+ T lymphocytes activation and interferon-γ (IFN-γ) production. In this study, we developed an effective and gene modified tumor cell vaccine. Lewis lung cancer cell LL/2 transfected with the DOTAP:cholesterol cationic liposome could express the mouse IL-27 (mIL-27) gene at a relative high level. The resultant transfectants were then irradiated with X-ray and used as a tumor cell vaccine. This tumor cell vaccine not only contained tumor associated antigen (TAA) of LL/2 cells but also secreted mIL-27 which could induce immune response in mice. The mice vaccinated with LL/2-mIL-27 performed strong tumor inhibiting effect accompanied with a high IFN-γ production. Both CD4+ and CD8+ T lymphocytes were significantly elevated in these mice vaccinated with LL/2-mIL-27 cell vaccine. Moreover, after depletion of CD4+, CD8+ T lymphocytes by injection of antibodies against CD4 and CD8, the vaccinated mice inoculated with autologous LL/2 cells were not protected from tumor challenge. In contrast, vaccinated mice inoculated with autologous LL/2 cells were treated with antibody against natural killer (NK)cells or normal rat IgG still possessed strong antitumor activity. Our data suggested that DOTAP:cholesterol cationic liposome was quite useful in generating an autologous tumor cell vaccine and mIL-27 could be therapeutically used to potentiate the host antitumor immunity.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Hongwei
authors.initials: H
authors.lastname: Tian
authors.forename: Can
authors.initials: C
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.forename: Ruibo
authors.initials: R
authors.lastname: Wang
authors.forename: Fen
authors.initials: F
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Dai
authors.forename: Gang
authors.initials: G
authors.lastname: Shi
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Chen
authors.forename: Yiming
authors.initials: Y
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Du
authors.forename: Jie
authors.initials: J
authors.lastname: Deng
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Hongxin
authors.initials: H
authors.lastname: Deng
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D005229:Fatty Acids, Monounsaturated; D005260:Female; D005818:Genetic Engineering / Q000379:methods*; D016219:Immunotherapy, Adoptive / Q000379:methods; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D000644:Quaternary Ammonium Compounds; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D014162:Transfection
chemical_list: D019496:Cancer Vaccines; D005229:Fatty Acids, Monounsaturated; C486767:Il27 protein, mouse; D007378:Interleukins; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane