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Regulatory T cell (Treg) depletion via Fc gamma receptor (FcγR)-mediated cytotoxicity involves monoclonal antibodies that bind to surface molecules highly expressed on Tregs, such as CTLA-4 or CD25. These antibodies are engineered with Fc regions optimized for binding to activating FcγRs on effector immune cells like macrophages and natural killer (NK) cells. This engagement triggers antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP), leading to selective elimination of the targeted Treg population within tissues, especially tumors, enhancing anti-tumor immunity.
Monoclonal antibody binds surface antigen on Tregs -> Engagement of Fc gamma receptor on effector cells -> Triggers ADCC/ADCP -> Treg depletion
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