Immunoglobulin G1 Fc region (IgG1 Fc)

The Immunoglobulin G1 (IgG1) Fc region is the tail portion of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system (Vidarsson et al., 2014). In oncology, the Fc region of tumor-targeting IgG1 antibodies is essential for bridging the adaptive immune response with the innate immune system. By binding to Fc gamma receptors (FcγRs) on natural killer cells and macrophages, the Fc region triggers antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), leading to the destruction of cancer cells (Wang et al., 2018). Additionally, the Fc region binds to the neonatal Fc receptor (FcRn), which protects the antibody from lysosomal degradation, thereby extending its half-life in the bloodstream to several weeks (Saunders, 2019). Therapeutic engineering of the Fc region, such as glycoengineering or amino acid substitutions, is frequently employed to enhance these effector functions or to modulate the antibody's pharmacokinetic profile for better clinical outcomes (Liu et al., 2020). The interaction between the Fc region and C1q also initiates the complement-dependent cytotoxicity (CDC) pathway, providing another mechanism for tumor cell lysis. Understanding the polymorphisms in Fc receptors that bind this region is crucial for predicting patient response to monoclonal antibody therapies. Safety concerns associated with Fc-mediated activity include systemic cytokine release and potential off-target immune activation.

Other names

Fc fragmentFragment crystallizable regionIgG1 Fc domainCH2-CH3 domain

The Fc region mediates tumor cell clearance by binding to Fc gamma receptors (FcγRs) on effector cells such as natural killer cells and macrophages to induce ADCC and ADCP, and by binding to C1q to activate the classical complement pathway (CDC). It also interacts with the neonatal Fc receptor (FcRn) to regulate antibody recycling and serum persistence.