Fcengineered

Fcengineered refers to antibodies and Fc fusion proteins whose constant Fc region has been deliberately modified to adjust interactions with Fc receptors and the complement system. The goal is to shape effector functions, pharmacokinetics, and safety by altering how the immune system recognizes and responds to the therapeutic molecule.

Common strategies include modifying Fc receptor engagement and complement activation. Afucosylation or specific Fc mutations can increase binding to Fc gamma receptor IIIa and enhance antibody-dependent cellular cytotoxicity (ADCC), while other mutations reduce Fc receptor binding to lessen effector activity. Alterations can also affect C1q binding to modulate complement-dependent cytotoxicity (CDC). Glycoengineering, which changes the sugar structures attached to the Fc, is a widely used approach to tune these properties. In parallel, formulations to extend serum half-life employ FcRn-binding mutations such as YTE (M252Y/M254T/T256E) and LS (M428L/N434S).

Applications are diverse and largely centered on cancer immunotherapy and autoimmune diseases. Fc engineering aims to increase tumor cell killing or, conversely, to suppress unwanted immune activation. It is also used in antibody-drug conjugates and Fc-fusion proteins to balance efficacy, safety, and dosing practicality.

Notable examples include obinutuzumab, a glycoengineered anti-CD20 antibody with afucosylated Fc to boost ADCC, and mogamulizumab, a defucosylated anti-CCR4 antibody with enhanced effector function. Fc engineering remains an active area of development, with ongoing research to optimize activity, pharmacokinetics, manufacturability, and immunogenicity considerations.