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.
|Publication status||Published - 2015|
Bibliographical noteThe information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Oncology, MV (013035000), Oncology, Kamprad Lab (013230901), Stem Cell Center (013041110), Division of Hematology and Transfusion Medicine (013041100), Tumour Biology, Malmö (013031300), Department of Experimental Medical Science (013210000), Medical Inflammation Research (013212019)
Department affilation moved from v1000588 (Tumour Biology, Malmö) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:39:28.
Subject classification (UKÄ)
- Cancer and Oncology