title: Antagonistic human FcγRIIB (CD32B) antibodies have anti-tumor activity and overcome resistance to antibody therapy in vivo.
abstract: Therapeutic antibodies have transformed cancer therapy, unlocking mechanisms of action by engaging the immune system. Unfortunately, cures rarely occur and patients display intrinsic or acquired resistance. Here, we demonstrate the therapeutic potential of targeting human (h) FcγRIIB (CD32B), a receptor implicated in immune cell desensitization and tumor cell resistance. FcγRIIB-blocking antibodies prevented internalization of the CD20-specific antibody rituximab, thereby maximizing cell surface accessibility and immune effector cell mediated antitumor activity. In hFcγRIIB-transgenic (Tg) mice, FcγRIIB-blocking antibodies effectively deleted target cells in combination with rituximab, and other therapeutic antibodies, from resistance-prone stromal compartments. Similar efficacy was seen in primary human tumor xenografts, including with cells from patients with relapsed/refractory disease. These data support the further development of hFcγRIIB antibodies for clinical assessment.
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: Ali
authors: A
authors: Roghanian
authors: BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
authors: Ingrid
authors: I
authors: Teige
authors: BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
authors: Linda
authors: L
authors: Mårtensson
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: Kerry L
authors: KL
authors: Cox
authors: BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
authors: Mathilda
authors: M
authors: Kovacek
authors: BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
authors: Anne
authors: A
authors: Ljungars
authors: BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
authors: Jenny
authors: J
authors: Mattson
authors: BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
authors: Annika
authors: A
authors: Sundberg
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: Andrew T
authors: AT
authors: Vaughan
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: Vallari
authors: V
authors: Shah
authors: Centre for Biological Sciences, University of Southampton, Southampton SO16 6YD, UK.
authors: Neil R
authors: NR
authors: Smyth
authors: Centre for Biological Sciences, University of Southampton, Southampton SO16 6YD, UK.
authors: Bhavwanti
authors: B
authors: Sheth
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: H T Claude
authors: HT
authors: Chan
authors: BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
authors: Zhan-Chun
authors: ZC
authors: Li
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: Emily L
authors: EL
authors: Williams
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: Giusi
authors: G
authors: Manfredi
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: Robert J
authors: RJ
authors: Oldham
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: C Ian
authors: CI
authors: Mockridge
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: Sonya A
authors: SA
authors: James
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: Lekh N
authors: LN
authors: Dahal
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: Khiyam
authors: K
authors: Hussain
authors: Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, 221 85 Lund, Sweden.
authors: Björn
authors: B
authors: Nilsson
authors: Department of Human Genetics, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
authors: J Sjef
authors: JS
authors: Verbeek
authors: Skåne University Hospital, Lund University, 221 84 Lund, Sweden.
authors: Gunnar
authors: G
authors: Juliusson
authors: Skåne University Hospital, Lund University, 221 84 Lund, Sweden.
authors: Markus
authors: M
authors: Hansson
authors: Skåne University Hospital, Lund University, 221 84 Lund, Sweden.
authors: Mats
authors: M
authors: Jerkeman
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: Peter W M
authors: PW
authors: Johnson
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: Andrew
authors: A
authors: Davies
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: Stephen A
authors: SA
authors: Beers
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
authors: Martin J
authors: MJ
authors: Glennie
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK; BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
authors: Björn
authors: B
authors: Frendéus
authors: Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK. Electronic address: msc@soton.ac.uk.
authors: Mark S
authors: MS
authors: Cragg
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D017452:Receptors, IgG / Q000037:antagonists & inhibitors* / Q000502:physiology; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C499173:FCGR2B protein, human; D017452:Receptors, IgG; D000069283:Rituximab