AI Article Synopsis
- Therapeutic antibodies have revolutionized cancer treatment by enhancing immune system engagement but often face challenges like resistance in patients.
- Targeting the human FcγRIIB receptor shows potential in overcoming this resistance by preventing the internalization of other therapeutic antibodies like rituximab, boosting their effectiveness against target cells.
- Research in hFcγRIIB-transgenic mice and human tumor models suggests that using FcγRIIB-blocking antibodies alongside existing treatments could help eliminate cancer cells more effectively, warranting further clinical investigation.
Article 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.
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| http://dx.doi.org/10.1016/j.ccell.2015.03.005 | DOI Listing |
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