Immunoglobulin G Fc region (IgG Fc) (IgG Fc)

The Immunoglobulin G Fc region (IgG Fc) on antibody-coated tumor cells serves as a critical molecular bridge between the adaptive and innate immune systems. When a therapeutic monoclonal antibody binds to a tumor-associated antigen via its Fab regions, the Fc region is exposed and oriented to interact with Fc gamma receptors (FcγRs) on effector cells such as natural killer (NK) cells, neutrophils, and macrophages (Wang et al., 2018, Nature Reviews Immunology). This interaction triggers potent anti-tumor mechanisms, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In the context of modern oncology, the Fc region is increasingly utilized as a universal target for 'adaptable' cellular therapies, such as CAR-T cells engineered with CD16 or other Fc-binding domains, which allow a single cell product to be redirected against multiple tumor types by switching the co-administered antibody (Kudo et al., 2014, Cancer Research). The efficacy of targeting this region can be significantly influenced by genetic polymorphisms in the patient's Fc receptors, such as the FCGR3A-158V/F variant, which dictates the binding affinity and subsequent immune response (Cartron et al., 2002, Blood). Furthermore, therapeutic strategies must account for the high concentration of endogenous IgG in circulation, which can compete for binding sites on effector cells or engineered receptors.

Other names

Fc fragment of IgGCrystallizable fragment of IgGIgG Fc domainAntibody Fc region

The IgG Fc region acts as a docking site for Fc gamma receptors (FcγRs) on immune effector cells or engineered CAR-T cells, facilitating the targeted lysis or phagocytosis of the tumor cell to which the antibody is bound (Kudo et al., 2014, Cancer Research).