title: Antitumor activity of lentivirus-mediated interleukin -12 gene modified dendritic cells in human lung cancer in vitro.
abstract: OBJECTIVE
  Dendritic cell (DC)-based tumor immunotherapy needs an immunogenic tumor associated antigen (TAA) and an effective approach for its presentation to lymphocytes. In this study we explored whether transduction of DCs with lentiviruses (LVs) expressing the human interleukin-12 gene could stimulate antigen- specific cytotoxic T cells (CTLs) against human lung cancer cells in vitro.
  
  
  METHODS
  Peripheral blood monocyte- derived DCs were transduced with a lentiviral vector encoding human IL-12 gene (LV-12). The anticipated target of the human IL-12 gene was detected by RT-PCR. The concentration of IL-12 in the culture supernatant of DCs was measured by ELISA.Transduction efficiencies and CD83 phenotypes of DCs were assessed by flow cytometry. DCs were pulsed with tumor antigen of lung cancer cells (DC+Ag) and transduced with LV-12 (DC-LV-12+Ag). Stimulation of T lymphocyte proliferation by DCs and activation of cytotoxic T-lymphocytes (CTL) stimulated by LV-12 transduced DCs pulsed with tumor antigen against A549 lung cancer cells were assessed with methyl thiazolyltetrazolium (MTT).
  
  
  RESULTS
  A recombinant lentivirus expressing the IL-12 gene was successfully constructed. DC transduced with LV-12 produced higher levels of IL-12 and expressed higher levels of CD83 than non-transduced. The DC modified by interleukin -12 gene and pulsed with tumor antigen demonstrated good stimulation of lymphocyte proliferation, induction of antigen-specific cytotoxic T lymphocytes and anti- tumor effects.
  
  
  CONCLUSIONS
  Dendritic cells transduced with a lentivirus-mediated interleukin-12 gene have an enhanced ability to kill lung cancer cells through promoting T lymphocyte proliferation and cytotoxicity.
authors.affiliation: Department of Central Research, Second Hospital, Jilin University, Changchun, China E-mail : zhanguizhenjlu@163.com, doom99106@163.com.
authors.forename: Hassan Abdellah
authors.initials: HA
authors.lastname: Ahmed Ali
authors.forename: Jun
authors.initials: J
authors.lastname: Di
authors.forename: Wu
authors.initials: W
authors.lastname: Mei
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Zhen-Wu
authors.initials: ZW
authors.lastname: Du
authors.forename: Gui-Zhen
authors.initials: GZ
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007167:Immunotherapy; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D019496:Cancer Vaccines; D012333:RNA, Messenger; D018664:Interleukin-12