Fc-Silenced Antibody Expression Service

At evitria, we ensure entirely Fc-silenced antibodies by utilizing mAbsolve’s STR technology, which involves specific amino acid substitutions in the Fc region of antibodies like human IgG1 and other variants. These substitutions, eliminate binding to Fc gamma receptors (FcγRs) such as FcγRI and FcγRIIIA. By engineering the Fc domain, we remove Fc-mediated effector functions like antibody-dependent cellular cytotoxicity (ADCC) and cytokine release. Our recombinant monoclonal antibodies (mAbs) are produced in CHO cell lines and undergo rigorous characterization to confirm their suitability for both in vitro and in vivo experiments

mAbsolve’s STR technology is based on engineering of the antibody’s Fc region to disrupt interactions with Fc gamma receptors. By introducing specific amino acid substitutions at key residues in the Fc domain, the technology prevents binding to FcγRs without affecting the Fab region’s ability to bind to epitopes on target antigens. This principle can be used to create  Fc fusion proteins and chimeric antibodies that are Fc-silenced. The STR mutations also minimize aggregation and maintain the antibody’s stability and half-life by not interfering with the neonatal Fc receptor (FcRn) interactions. This advanced form of Fc engineering is crucial for creating therapeutic antibodies with reduced side effects and improved safety profiles.

Fc-silenced antibodies are essential in therapeutic and research applications where activation of the immune system could be detrimental. In cancer research, for example, they allow scientists to target cancer cells without triggering immune effector functions that could harm healthy tissues. In immunotherapy, these antibodies can block specific receptors or ligands on target cells without inducing ADCC or other Fc-mediated activities. They are also valuable in in vitro assays to study antigen-antibody interactions without interference from immune cells. By eliminating unwanted effector functions, Fc-silenced antibodies reduce potential side effects and provide clearer insights into biological processes.

The activity of the Fc region is determined by its ability to bind to Fc gamma receptors (FcγRs) on immune cells, which is influenced by the specific amino acid sequence and glycosylation patterns of the Fc domain. Variations in IgG subclasses (e.g., IgG1 Fc vs. IgG2 Fc) and specific residues can alter binding affinity to receptors like FcγRI and FcγRIIIA. Factors such as Fc glycosylation, aggregation, and the presence of mutations or substitutions also impact Fc-mediated effector functions like ADCC. Additionally, interactions with the neonatal Fc receptor (FcRn) affect the antibody’s half-life and pharmacokinetics. By carefully engineering these elements, we can modulate the Fc region’s activity to meet your specific therapeutic or research needs.