Monoclonal antibodies are essential tools for many molecular immunology investigations. They are laboratory-produced molecules designed to replace antibodies that can restore, enhance or mimic the immune system's attack on cancer cells. There are usually two ways to kill or induce the death of target cells. One is to rely on the Fab fragments to specifically identify the relevant antigens on the surface of target cells, and regulate and interfere with the signaling pathways mediated by antigen receptors. The other is to further improve the therapeutic effect of the antibody by the binding of its Fc region to the Fc gamma receptor (FcγR) or other ligands on the surface of immune cells.

The IgG antibody consists of two Fab fragments and one crystallizable fragment (Fc) region. The Fab fragment can specifically identify molecular targets and bind to specific proteins and receptors on the cell surface, while the Fc region can propagate a range of effector responses. There are five types of Fc receptors of IgG molecules in the human body: FcγRI(CD64), FcγRII (CD32a, B, C), FcγRIII(CD16a, B,c), neonatal Fc receptor (FcRn) and C1 complement complex (C1q).

By interacting with these cell receptors, antibodies have the unique functions, including ADCC/ADCP activity, CDC activity, agonistic activity, and endosomal recycling. Therapeutic Fc engineering technology is an attractive approach that allows researchers to enhance the function of existing antibodies for maximum therapeutic effect.

※ Enhancing CDC Activity
CDC is an effective effect mechanism involving innate immunity and adaptive immunity. The main strategy to improve the CDC activity of antibody therapeutics mainly focused on enhancing the interaction between the antibody Fc and the C1q. The glycans attached at the N297 residue in the Fc region are crucial for efficient binding to FcγR and C1q, and because this residue can enhance CDC activities and Fc–C1q interactions.

※ Enhancing ADCC/ADCP activity
FcγR has the potential to affect the efficacy of anti-cancer antibodies. When it binds to the Fc region of the antibody, it can activate ADCC and ADCP activities. Currently, engineering mutations in the Fc region mainly focus on enhancing the effector function of ADCC/ADCP by improving the binding ability of Fc and activated FcγR. This technique is achieved by amino acid mutation and glycosylation modification.

※ Fc engineering for serum half-life regulation
The serum half-life of IgG antibodies is regulated by a cellular receptor, named the FcRn. Fc is the region that interacts with the FcRn, which can save the intracellular degradation of IgG and prolong its serum half-life.

※ Enhanced FcγRIIb Binding Affinity
FcγRIIb is the only inhibitory FcγR. Recently, it has been reported that adding inhibitory FcγRIIb through the Fc region is an attractive method to improve the efficacy and function of antibody drugs. By using therapeutic Fc engineering technology, the Fc–FcγR interaction can be modulated to enhance the potency of antibodies that target membrane-bound antibodies. For tumor-targeting antibodies, FcγRIIb expression is associated with reduced antibody efficacy. For example, highly expressed FcγRIIb can reduce the activity of rituximab.

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