Antonio Pérez-Martínez1, Jaime Valentín2, Lucía Fernández3, Enrique Hernández-Jiménez2, Eduardo López-Collazo2, Petra Zerbes4, Ellen Schwörer4, Fernando Nuñéz5, Inmaculada Génesis Martín5, Hannah Sallis6, Miguel Ángel Díaz7, Rupert Handgretinger4, Matthias Manuel Pfeiffer4. 1. 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. 2. Innate Immune Research Group, Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain. 3. Clinical Research Program, Cancer Research National Centre, Madrid, Spain. 4. University Children's Hospital, University of Tuebingen, Tuebingen, Germany. 5. Servicio Experimentación Animal. Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas Madrid, Spain. 6. School of Medicine, Cardiff University, Heath Park, Cardiff, Wales. 7. Department of Hemato-Oncology and Stem Cell Transplantation, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Abstract
BACKGROUND AIMS: 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.
BACKGROUND AIMS: 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: Soo Liang Ooi; Sok Cheon Pak; Peter S Micalos; Emily Schupfer; Rob Zielinski; Thomas Jeffries; Garth Harris; Terry Golombick; David McKinnon Journal: Contemp Clin Trials Commun Date: 2020-05-29