title: A Cytokine Cocktail Augments the Efficacy of Adoptive NK-92 Cell Therapy Against Mouse Xenografts of Human Cancer.
abstract: OBJECTIVE
  Peripheral blood mononuclear cells (PBMCs) activated with immobilized monoclonal antibody against cluster of differentiation 3 (CD3) secrete cytokines in their culture supernatant (termed ACD3S). We examined the antitumor efficacy of ACD3S-activated NK-92 cells in vitro and in vivo.
  
  
  METHODS
  Interleukin (IL) 2-depleted NK-92 cells were reactivated with ACD3S, analyzed for their phenotype and tested for cytotoxicity, and perforin and interferon γ (IFNγ) production. Severe combined immunodeficient (SCID) mice xenografted with human melanoma and breast cancer cells were treated with ACD3S-activated NK-92 cells and tumor growth was monitored.
  
  
  RESULTS
  Brief activation of IL2-depleted NK-92 cells with ACD3S fully restored their in vitro cytotoxicity towards tumor cells. ACD3S-activated NK-92 cells were phenotypically similar to standard NK-92 cells, but exhibited prolonged cytotoxicity and produced higher levels of IFNγ. When adoptively transferred to tumor-bearing SCID mice, these cells retarded the growth of melanoma and breast tumors.
  
  
  CONCLUSIONS
  Stimulation of NK-92 cells with ACD3S may be useful in clinical cancer therapy, as an alternative method for ex vivo natural killer cell activation.
authors.affiliation: Department of Animal and Human Physiology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece rtsitsil@biol.uoa.gr psamara@biol.uoa.gr.
authors.forename: Pinelopi
authors.initials: P
authors.lastname: Samara
authors.affiliation: Department of Animal and Human Physiology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Margarita
authors.initials: M
authors.lastname: Skopeliti
authors.affiliation: Department of Animal and Human Physiology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece Department of Clinical Therapeutics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Marinos L
authors.initials: ML
authors.lastname: Tsiatas
authors.affiliation: Department of Animal and Human Physiology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Sylvianna
authors.initials: S
authors.lastname: Georgaki
authors.affiliation: Second Peripheral Blood Transfusion and Hemophilia Center, Laikon General Hospital, Athens, Greece.
authors.forename: Charilaos
authors.initials: C
authors.lastname: Gouloumis
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Voelter
authors.affiliation: Department of Clinical Therapeutics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Athanassios-Meletios
authors.initials: AM
authors.lastname: Dimopoulos
authors.affiliation: Department of Clinical Therapeutics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Aristotle
authors.initials: A
authors.lastname: Bamias
authors.affiliation: Department of Animal and Human Physiology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece rtsitsil@biol.uoa.gr psamara@biol.uoa.gr.
authors.forename: Ourania E
authors.initials: OE
authors.lastname: Tsitsilonis
mesh_terms: D000818:Animals; D055910:Antibodies, Immobilized / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D017252:CD3 Complex / Q000276:immunology; D016207:Cytokines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology; D061986:MCF-7 Cells; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
chemical_list: D055910:Antibodies, Immobilized; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines
keywords: Conditioned medium; NK-92; SCID mice; cytotoxicity