| Literature DB >> 25873171 |
Ali Roghanian1, Ingrid Teige2, Linda Mårtensson2, Kerry L Cox1, Mathilda Kovacek2, Anne Ljungars2, Jenny Mattson2, Annika Sundberg2, Andrew T Vaughan1, Vallari Shah1, Neil R Smyth3, Bhavwanti Sheth3, H T Claude Chan1, Zhan-Chun Li2, Emily L Williams1, Giusi Manfredi1, Robert J Oldham1, C Ian Mockridge1, Sonya A James1, Lekh N Dahal1, Khiyam Hussain1, Björn Nilsson4, J Sjef Verbeek5, Gunnar Juliusson6, Markus Hansson6, Mats Jerkeman6, Peter W M Johnson1, Andrew Davies1, Stephen A Beers1, Martin J Glennie1, Björn Frendéus7, Mark S Cragg8.
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.Entities:
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Year: 2015 PMID： 25873171 DOI： 10.1016/j.ccell.2015.03.005
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743