Fragment crystallizable region of tumor-bound antibodies (Fc region)

The Fragment crystallizable (Fc) region of tumor-bound antibodies is the constant C-terminal portion of an immunoglobulin molecule that remains exposed after the antibody's variable (Fab) regions have attached to a tumor-associated antigen [6, 19]. This region serves as a critical molecular scaffold that flags the tumor cell for destruction by the innate immune system [1, 10]. It functions by binding to various Fc-gamma receptors (FcγRs) on the surface of effector cells, such as natural killer (NK) cells, macrophages, and neutrophils, thereby initiating antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) [3, 12, 18]. Additionally, the Fc region can bind the C1q component of the complement system to trigger complement-dependent cytotoxicity (CDC) [9, 10]. In modern oncology, the Fc region is a primary focus for therapeutic optimization; antibodies like margetuximab and obinutuzumab are engineered with specific mutations or glycan profiles to enhance their affinity for activating FcγRs, such as CD16a, while reducing binding to inhibitory receptors like CD32b [5, 13, 16]. Furthermore, next-generation therapies like FT516 utilize engineered NK cells with high-affinity Fc receptors to specifically target the Fc region of any bound antibody, creating a versatile platform for treating multiple cancer types [2, 11].

Other names

Fc fragmentConstant region of immunoglobulinIgG Fc domainAntibody stemEffector domain of tumor-bound IgG

Engagement of Fc-gamma receptors (FcγRs) on immune effector cells or activation of the complement system to induce lysis or phagocytosis of the antibody-coated tumor cell.