Antagonistic human FcγRIIB (CD32B) antibodies have anti-tumor activity and overcome resistance to antibody therapy in vivo
| Autor: | Markus Hansson, C. Ian Mockridge, Robert J. Oldham, Björn Frendéus, Björn Nilsson, Neil Smyth, Ali Roghanian, Vallari Shah, Lekh N. Dahal, Jenny Mattson, Stephen A. Beers, Zhan-Chun Li, Mathilda Kovacek, Peter Johnson, Kerry L. Cox, Annika Sundberg, Linda Mårtensson, Ingrid Teige, H.T. Claude Chan, Khiyam Hussain, Anne Ljungars, Andrew T M Vaughan, Sonya James, Martin J. Glennie, Bhavwanti Sheth, J. Sjef Verbeek, Mats Jerkeman, Giusi Manfredi, Emily L Williams, Gunnar Juliusson, Andrew Davies, Mark S. Cragg |
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| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Stromal cell media_common.quotation_subject Cell Biology Antibodies Monoclonal Murine-Derived Mice Immune system Neoplasms medicine Animals Humans Internalization media_common Antibody-dependent cell-mediated cytotoxicity Receptors IgG Antibodies Monoclonal Drug Synergism Cell Biology medicine.anatomical_structure Oncology Immunology Monoclonal biology.protein Rituximab Antibody medicine.drug |
| Zdroj: | Cancer Cell, 27(4), 473-488 |
| ISSN: | 1878-3686 |
| Popis: | SummaryTherapeutic 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. |
| Databáze: | OpenAIRE |
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