The Fc Fragment of IgG Receptor and Transporter (FCGRT) is a pivotal protein facilitating the transfer of passive humoral immunity from mother to fetus across the placenta, also called FcRn. FCGRT binds to the Fc region of immunoglobulin G (IgG), shielding the antibody from degradation and facilitating its selective uptake from milk. Throughout life, FCGRT plays a crucial role in maintaining effective humoral immunity by recycling IgG and prolonging its half-life in circulation. Additionally, FCGRT is involved in regulating the homeostasis of albumin, the other most abundant circulating protein.

Its Gene ID: 2217, UniProtKB ID: P55899, and OMIM ID: 601437.

FCGRT-Mediated Transport Pathways

FCGRT is widely expressed across diverse cell types and organs throughout the body. Utilizing two distinct pathways—cellular recycling and transcytosis—the neonatal Fc receptor efficiently transports its ligands. IgG and albumin undergo internalization via pinocytosis into early endosomes. FCGRT, primarily localized in acidified endosomes, binds these ligands within recycling compartments and facilitates their recycling back to the cell surface, culminating in ligand exocytosis. Ligands that do not bind to FCGRT undergo sorting to late endosomes and lysosomes, where they undergo degradation. Additionally, in polarized epithelial cell layers, FCGRT-mediated bidirectional transport ensues.

Fig.1 Schematic diagram of FCGRT-mediated transport pathways.¹

Exploring Therapeutic Strategies: Anti-FCGRT Antibodies in Immune Regulation

FCGRT plays a central role in regulating the homeostasis of IgG and albumin across an individual's lifetime, with increasing acknowledgment of its importance in surveillance mucosal immunity, tumor immunity, and autoimmune diseases. Diverse engineering strategies have been devised to manipulate the FCGRT-mediated transport pathway, aiming to create enduring and minimally invasive therapeutics. One such approach involves the design of anti-FCGRT antibodies.

• Anti-FCGRT Inhibitor Antibody in MG Therapy

In the autoimmune condition of myasthenia gravis (MG), pathogenicity predominantly stems from detrimental antibodies, necessitating the longstanding use of Ig removal and reduction in therapeutic strategies. The innovative approach of targeting the FCGRT specifically using engineered high-affinity antibodies to enhance IgG degradation and accelerate catabolism presents a promising avenue for more effective and tailored therapeutic interventions with reduced adverse effects. In preclinical animal models of MG, monoclonal anti-FCGRT antibodies have demonstrated dose-dependent amelioration of the disease course by effectively reducing serum levels of pathogenic Abs.

Fig.2 Mechanism of FcRn (FCGRT) targeting.²

<> Creative Biolabs offers a comprehensive range of anti-FCGRT antibody products, meticulously crafted using recombinant techniques. Additionally, customization options are available to tailor FCGRT-based recombinant antibodies or neutralizing anttibodies, addressing specific needs with precision.

REFERENCES

1. Sand, Kine Marita Knudsen, et al. "Unraveling the interaction between FcRn and albumin: opportunities for design of albumin-based therapeutics." Frontiers in immunology 5 (2015): 118912.
2. Keller, Christian W., et al. "Fc-receptor targeted therapies for the treatment of myasthenia gravis." International Journal of Molecular Sciences 22.11 (2021): 5755.