title: Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma.
abstract: Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival times. The efficacy of current systemic therapies for HCC is limited. In this study, we used xenograft tumor models to investigate the use of antibodies that block CD47 and inhibit HCC tumor growth. Immunostaining of tumor tissue and HCC cell lines demonstrated CD47 over-expression in HCC as compared to normal hepatocytes. Macrophage phagocytosis of HCC cells was increased after treatment with CD47 antibodies (CD47mAbs) that block CD47 binding to SIRPα. Further, CD47 blockade inhibited tumor growth in both heterotopic and orthotopic models of HCC, and promoted the migration of macrophages into the tumor mass. Our results demonstrate that targeting CD47 by specific antibodies has potential immunotherapeutic efficacy in human HCC.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Haniee
authors.initials: H
authors.lastname: Chung
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Babak
authors.initials: B
authors.lastname: Banan
authors.affiliation: Vasculox, Inc., St. Louis, MO, USA.
authors.forename: Pamela T
authors.initials: PT
authors.lastname: Manning
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Ott
authors.affiliation: Department of Cardiovascular Medicine, Stanford University, Palo Alto, CA, USA.
authors.forename: Shin
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Capoccia
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Vijay
authors.initials: V
authors.lastname: Subramanian
authors.affiliation: Vasculox, Inc., St. Louis, MO, USA.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Hiebsch
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Gundumi A
authors.initials: GA
authors.lastname: Upadhya
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Thalachallour
authors.initials: T
authors.lastname: Mohanakumar
authors.affiliation: Departments of Biochemistry and Molecular Biophysics, Cell Biology, and Physiology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Frazier
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: liny@wudosis.wustl.edu.
authors.forename: Yiing
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: chapmanwi@wudosis.wustl.edu.
authors.forename: William C
authors.initials: WC
authors.lastname: Chapman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000918:Antibody Specificity; D051928:CD47 Antigen / Q000096:biosynthesis / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy*; D002465:Cell Movement / Q000276:immunology; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D010587:Phagocytosis / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D051928:CD47 Antigen; C497894:CD47 protein, human
keywords: Antibody therapy; CD47; HCC; Xenograft models