What are FcRn inhibitors?
The neonatal fragment crystallizable (Fc) receptor (FcRn) functions as a recycling mechanism to prevent degradation and extend the half-life of IgG and albumin in the circulation. Several FcRn inhibitors selectively targeting IgG recycling are now moving rapidly toward clinical practice in neurology and hematology.
Is rituximab specific or nonspecific?
Rituximab is a chimeric mouse/human monoclonal antibody (mAb) therapy with binding specificity to CD20. It was the first therapeutic antibody approved for oncology patients and was the top-selling oncology drug for nearly a decade with sales reaching $8.58 billion in 2016.
What does FcRn stand for?
FCRN
| Acronym | Definition |
|---|---|
| FCRN | Fluxnet-Canada Research Network (est. 2002) |
| FCRN | Feminist Crime Research Network (UK) |
| FCRN | Funds Classification Reference Number |
How does Efgartigimod work?
Efgartigimod is the Fc portion of an antibody that Argenx’ scientists have modified to increase its affinity for IgGs beyond that of normal antibodies. As a result, efgartigimod binds to IgG antibodies, including those that cause MG symptoms.
Why does IgG have long half-life?
IgGs experience high serum half-life due to the protective FcRn recycling pathway. Adapted from Roopenian et al., 2007.
What is FcRn antibody?
The neonatal Fc receptor for IgG (FcRn) is responsible for the transfer of passive humoral immunity from the mother to the newborn in rodents and humans. Throughout life, FcRn contributes to effective humoral immunity by recycling IgG and extending its half-life in the circulation.
Is rituximab active or passive?
The champion of passive immunotherapy to date is the anti-CD20 monoclonal antibody rituximab that revolutionized the standard of care for lymphoma.
What type of drug is Efgartigimod?
Efgartigimod (ARGX-113) is an investigational drug for IgG-mediated autoimmune diseases, consisting of an IgG1 Fc portion that has been mutated at 5 residues, ABDEG (antibodies that enhance IgG degradation) mutations, to increase its FcRn affinity at both physiologic and acidic pH.
How many days is half-life of IgG antibodies?
For total IgG, the half-life found was 25.8 days; for IgG1 it was 29.7 days; for IgG2 it was 26.9 days; and for IgG3 it was 15.7 days. The results are similar to those reported for endogeneous IgG. Half-lives for antibodies to S.
How are Fab arms involved in FcRn binding?
Recent work has indicated that in addition to the core Fc binding site on IgG, the fragment antigen binding (Fab) arms are also involved in FcRn binding ( 40 – 43 ). This was first suggested by experiments where antibodies with identical Fc but different Fab regions showed different affinity for FcRn and circulating half-life ( 40, 41 ).
What is the interaction between FcRn and IgG?
These results suggest that functional interaction of FcRn with monomeric IgG occurs with a 2:1 stoichiometry. Recent work has indicated that in addition to the core Fc binding site on IgG, the fragment antigen binding (Fab) arms are also involved in FcRn binding ( 40 – 43 ).
Can a immobilized receptor be used to detect FcRn?
Nevertheless, surface plasmon resonance (SPR) studies with immobilized receptor could not detect differences in FcRn binding kinetics for IgG variants with different variable domains and different isoelectric points ( 39 ).
How is the function of the FcRn determined?
Finally, the functions of FcRn are differentially determined by whether IgG is a single molecule, and thus monomeric, or present as an immune complex (IC). In the latter case, FcRn has been shown to critically regulate the innate immune responses as well as processing and presentation of antigens contained within IgG IC.