title: Arabinoxylan rice bran (MGN-3/Biobran) enhances natural killer cell-mediated cytotoxicity against neuroblastoma in vitro and in vivo.
abstract: OBJECTIVE
  Natural killer cell (NK) cytotoxic activity plays a major role in natural immunologic defences against malignancies. NK cells are emerging as a tool for adoptive cancer immunotherapies. Arabinoxylan rice bran (MGN-3/Biobran) has been described as a biological response modifier that can enhance the cytotoxic activity of NK cells. This study evaluated the effect of MGN-3/Biobran on NK cell activation, expansion and cytotoxicity against neuroblastoma cells.
  
  
  METHODS
  NK cells were enriched with magnetic beads and stimulated with MGN-3/Biobran. NK cell activation was evaluated via analysis of their phenotype, and their expansion capability was tracked. The in vitro cytotoxic ability of the activated NK cells was tested against K562, Jurkat, A673, NB1691, A-204, RD and RH-30 cell lines and the in vivo cytotoxic ability against the NB1691 cell line.
  
  
  RESULTS
  MGN-3/Biobran stimulation of NK cells induced a higher expression of the activation-associated receptors CD25 and CD69 than in unstimulated cells (P < 0.05). The expression of NKG2D, DNAM, NCRs and TLRs remained unchanged. Overnight MGN-3/Biobran stimulation increased NK cell cytotoxic activity against all cell lines tested in vitro and decelerated neuroblastoma growth in vivo. The mechanism is not mediated by lipopolysaccharide contamination in MGN-3/Biobran. Furthermore, the addition of MGN-3/Biobran promoted NK cell expansion and decreased T cells in vitro.
  
  
  CONCLUSIONS
  Our data show that MGN-3/Biobran upregulates NK cell activation markers, stimulates NK cell cytotoxic activity against neuroblastoma in vitro and in vivo and selectively augments the expansion of NK cells. These results may be useful for future NK cell therapeutic strategies of the treatment of neuroblastoma.
authors.affiliation: Department of Pediatric Hemato-Oncology, Hospital Universitario La Paz, Madrid, Spain; Innate Immune Research Group, Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain. Electronic address: aperezmartinez@salud.madrid.org.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pérez-Martínez
authors.affiliation: Innate Immune Research Group, Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Valentín
authors.affiliation: Clinical Research Program, Cancer Research National Centre, Madrid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Fernández
authors.affiliation: Innate Immune Research Group, Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Hernández-Jiménez
authors.affiliation: Innate Immune Research Group, Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Collazo
authors.affiliation: University Children's Hospital, University of Tuebingen, Tuebingen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Zerbes
authors.affiliation: University Children's Hospital, University of Tuebingen, Tuebingen, Germany.
authors.forename: Ellen
authors.initials: E
authors.lastname: Schwörer
authors.affiliation: Servicio Experimentación Animal. Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Nuñéz
authors.affiliation: Servicio Experimentación Animal. Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas Madrid, Spain.
authors.forename: Inmaculada Génesis
authors.initials: IG
authors.lastname: Martín
authors.affiliation: School of Medicine, Cardiff University, Heath Park, Cardiff, Wales.
authors.forename: Hannah
authors.initials: H
authors.lastname: Sallis
authors.affiliation: Department of Hemato-Oncology and Stem Cell Transplantation, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Díaz
authors.affiliation: University Children's Hospital, University of Tuebingen, Tuebingen, Germany.
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.affiliation: University Children's Hospital, University of Tuebingen, Tuebingen, Germany.
authors.forename: Matthias Manuel
authors.initials: MM
authors.lastname: Pfeiffer
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004195:Disease Models, Animal; D005453:Fluorescence; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology* / Q000187:drug effects; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009447:Neuroblastoma / Q000276:immunology* / Q000473:pathology; D012275:Oryza / Q000737:chemistry*; D055607:Receptors, Natural Killer Cell / Q000378:metabolism; D014990:Xylans / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D055607:Receptors, Natural Killer Cell; D014990:Xylans; C419427:polysaccharide MGN3; C085118:arabinoxylan
keywords: arabinoxylan rice bran (MGN-3/Biobran); cytotoxic activity; natural killer (NK) cells; neuroblastoma