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Antagonistic Human FcγRIIB (CD32B) Antibodies Have Anti-Tumor Activity and Overcome Resistance to Antibody Therapy In Vivo.

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Author

  • Ali Roghanian
  • Ingrid Teige
  • Linda Mårtensson
  • Kerry L Cox
  • Mathilda Kovacek
  • Anne Ljungars
  • Jenny Mattson
  • Annika Sundberg
  • Andrew T Vaughan
  • Vallari Shah
  • Neil R Smyth
  • Bhavwanti Sheth
  • H T Claude Chan
  • Zhan-Chun Li
  • Emily L Williams
  • Giusi Manfredi
  • Robert J Oldham
  • C Ian Mockridge
  • Sonya A James
  • Lekh N Dahal
  • Khiyam Hussain
  • Björn Nilsson
  • J Sjef Verbeek
  • Gunnar Juliusson
  • Markus Hansson
  • Mats Jerkeman
  • Peter W M Johnson
  • Andrew Davies
  • Stephen A Beers
  • Martin J Glennie
  • Björn Frendéus
  • Mark S Cragg
Show all

Summary, in English

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.

Department/s

Publishing year

2015

Language

English

Pages

473-488

Publication/Series

Cancer Cell

Volume

27

Issue

4

Document type

Journal article

Publisher

Cell Press

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Lymphoma - Clinical Research
  • Myeloma research group

ISBN/ISSN/Other

  • ISSN: 1878-3686