Serum immunoglobulin and the threshold of Fc receptor-mediated immune activation.
Antibody structure
Effector functions
Fc
Fc receptors
Glycosylation
Immunoglobulin
Therapeutic antibodies
Journal
Biochimica et biophysica acta. General subjects
ISSN: 1872-8006
Titre abrégé: Biochim Biophys Acta Gen Subj
Pays: Netherlands
ID NLM: 101731726
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
received:
05
07
2023
revised:
23
08
2023
accepted:
23
08
2023
medline:
9
10
2023
pubmed:
1
9
2023
entrez:
31
8
2023
Statut:
ppublish
Résumé
Antibodies can mediate immune recruitment or clearance of immune complexes through the interaction of their Fc domain with cellular Fc receptors. Clustering of antibodies is a key step in generating sufficient avidity for efficacious receptor recognition. However, Fc receptors may be saturated with prevailing, endogenous serum immunoglobulin and this raises the threshold by which cellular receptors can be productively engaged. Here, we review the factors controlling serum IgG levels in both healthy and disease states, and discuss how the presence of endogenous IgG is encoded into the functional activation thresholds for low- and high-affinity Fc receptors. We discuss the circumstances where antibody engineering can help overcome these physiological limitations of therapeutic antibodies. Finally, we discuss how the pharmacological control of Fc receptor saturation by endogenous IgG is emerging as a feasible mechanism for the enhancement of antibody therapeutics.
Identifiants
pubmed: 37652365
pii: S0304-4165(23)00146-0
doi: 10.1016/j.bbagen.2023.130448
pii:
doi:
Substances chimiques
Receptors, Fc
0
Immunoglobulin G
0
Receptors, IgG
0
Immunoglobulin Fc Fragments
0
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
130448Subventions
Organisme : Cancer Research UK
ID : A24721
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : U01 AI148153
Pays : United States
Informations de copyright
Copyright © 2023. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest S.A.B. has acted as a consultant for a number of biotechs and receives institutional support for grants and patents from BioInvent. M.C. has acted as a consultant for a number of biotechs and legal firms and is a named inventor on a patent application describing “Combined therapeutic use of antibodies and endoglycosidases” (WO2013110946A1) which was acquired by Hansa Biopharma.