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Cancer Cell. 2015 Apr 13;27(4):473-88. doi: 10.1016/j.ccell.2015.03.005.

Antagonistic human FcγRIIB (CD32B) antibodies have anti-tumor activity and overcome resistance to antibody therapy in vivo.

Author information

1
Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
2
BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
3
Centre for Biological Sciences, University of Southampton, Southampton SO16 6YD, UK.
4
Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, 221 85 Lund, Sweden.
5
Department of Human Genetics, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
6
Skåne University Hospital, Lund University, 221 84 Lund, Sweden.
7
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.
8
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.

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.

PMID:
25873171
DOI:
10.1016/j.ccell.2015.03.005
[Indexed for MEDLINE]
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