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In Translation: FcRn across the Therapeutic Spectrum.
Qi, Timothy; Cao, Yanguang.
  • Qi T; Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, Chapel Hill, NC 27599, USA.
  • Cao Y; Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, Chapel Hill, NC 27599, USA.
Int J Mol Sci ; 22(6)2021 Mar 17.
Article in English | MEDLINE | ID: covidwho-1389395
ABSTRACT
As an essential modulator of IgG disposition, the neonatal Fc receptor (FcRn) governs the pharmacokinetics and functions many therapeutic modalities. In this review, we thoroughly reexamine the hitherto elucidated biological and thermodynamic properties of FcRn to provide context for our assessment of more recent advances, which covers antigen-binding fragment (Fab) determinants of FcRn affinity, transgenic preclinical models, and FcRn targeting as an immune-complex (IC)-clearing strategy. We further comment on therapeutic antibodies authorized for treating SARS-CoV-2 (bamlanivimab, casirivimab, and imdevimab) and evaluate their potential to saturate FcRn-mediated recycling. Finally, we discuss modeling and simulation studies that probe the quantitative relationship between in vivo IgG persistence and in vitro FcRn binding, emphasizing the importance of endosomal transit parameters.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Fc / Histocompatibility Antigens Class I Type of study: Experimental Studies Limits: Animals / Humans Language: English Year: 2021 Document Type: Article Affiliation country: IJMS22063048

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Fc / Histocompatibility Antigens Class I Type of study: Experimental Studies Limits: Animals / Humans Language: English Year: 2021 Document Type: Article Affiliation country: IJMS22063048