Immunoglobulin G1 Fc region (IgG1 Fc) (IgG1 Fc)

The IgG1 Fc region of rituximab is the crystallizable fragment of the chimeric monoclonal antibody, consisting of the CH2 and CH3 constant domains of the human IgG1 heavy chain [1]. This region is not a biological target in the traditional sense but is the effector component of the drug that mediates its therapeutic activity by interacting with the host's immune system [2]. Specifically, it binds to Fc gamma receptors (FcγRs) such as CD16a (FcγRIIIa) on natural killer cells to induce antibody-dependent cellular cytotoxicity (ADCC) and to CD32 (FcγRIIa) or CD64 (FcγRI) on myeloid cells for antibody-dependent cellular phagocytosis (ADCP) [1, 2]. It also binds the C1q protein to activate the classical complement pathway, leading to complement-dependent cytotoxicity (CDC) against CD20-positive B cells [2]. Additionally, the Fc region's interaction with the neonatal Fc receptor (FcRn) is responsible for the long serum half-life of rituximab by protecting it from lysosomal degradation and facilitating recycling [4]. Genetic variations in the host's Fc receptors, such as the FCGR3A V158F polymorphism, can significantly influence the binding affinity of the rituximab Fc region and thus its clinical efficacy [3]. While essential for the drug's action, the IgG1 Fc region is a structural component of the therapeutic agent itself rather than a disease-associated protein target [1]. Engineering of this region is a common strategy in drug development to enhance effector functions or extend the duration of action of monoclonal antibodies [2].

Other names

Fc fragment of IgG1Crystallizable fragment of IgG1CH2-CH3 domains of IgG1Constant region of IgG1 heavy chain

The IgG1 Fc region mediates effector functions (ADCC, ADCP, CDC) by binding to Fc gamma receptors and C1q, and regulates half-life via FcRn binding.