title: Targeting Tumor Cells with Anti-CD44 Antibody Triggers Macrophage-Mediated Immune Modulatory Effects in a Cancer Xenograft Model.
abstract: CD44, a transmembrane receptor reported to be involved in various cellular functions, is overexpressed in several cancer types and supposed to be involved in the initiation, progression and prognosis of these cancers. Since the sequence of events following the blockage of the CD44-HA interaction has not yet been studied in detail, we profiled xenograft tumors by RNA Sequencing to elucidate the mode of action of the anti-CD44 antibody RG7356. Analysis of tumor and host gene-expression profiles led us to the hypothesis that treatment with RG7356 antibody leads to an activation of the immune system. Using cytokine measurements we further show that this activation involves the secretion of chemo-attractants necessary for the recruitment of immune cells (i.e. macrophages) to the tumor site. We finally provide evidence for antibody-dependent cellular phagocytosis (ADCP) of the malignant cells by macrophages.
authors.affiliation: Translational Technologies and Bioinformatics, Pharmaceutical Sciences, Roche Innovation Center Munich, Penzberg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Maisel
authors.affiliation: Translational Technologies and Bioinformatics, Pharmaceutical Sciences, Roche Innovation Center Munich, Penzberg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Birzele
authors.affiliation: Discovery Oncology, Roche Innovation Center Munich, Penzberg, Germany.
authors.forename: Edgar
authors.initials: E
authors.lastname: Voss
authors.affiliation: Discovery Oncology, Roche Innovation Center Munich, Penzberg, Germany.
authors.forename: Adam
authors.initials: A
authors.lastname: Nopora
authors.affiliation: Translational Technologies and Bioinformatics, Pharmaceutical Sciences, Roche Innovation Center Munich, Penzberg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Bader
authors.affiliation: Discovery Oncology, Roche Innovation Center Munich, Penzberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Friess
authors.affiliation: Discovery Oncology, Roche Innovation Center Munich, Penzberg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Goller
authors.affiliation: Selventa Inc., Cambridge, Massachusetts, 02140, United States of America.
authors.forename: Daphna
authors.initials: D
authors.lastname: Laifenfeld
authors.affiliation: Large Molecule Research, Roche Innovation Center Basel, Basel, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Weigand
authors.affiliation: Discovery Oncology, Roche Innovation Center Munich, Penzberg, Germany.
authors.forename: Valeria
authors.initials: V
authors.lastname: Runza
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology; D010587:Phagocytosis
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D018960:Hyaluronan Receptors; C576196:RG7356