In vivo pharmacokinetic enhancement of monomeric Fc and monovalent bispecific designs through structural guidance.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
08 09 2021
08 09 2021
Historique:
received:
05
05
2020
accepted:
18
08
2021
entrez:
9
9
2021
pubmed:
10
9
2021
medline:
15
12
2021
Statut:
epublish
Résumé
In a biologic therapeutic landscape that requires versatility in targeting specificity, valency and half-life modulation, the monomeric Fc fusion platform holds exciting potential for the creation of a class of monovalent protein therapeutics that includes fusion proteins and bispecific targeting molecules. Here we report a structure-guided approach to engineer monomeric Fc molecules to adapt multiple versions of half-life extension modifications. Co-crystal structures of these monomeric Fc variants with Fc neonatal receptor (FcRn) shed light into the binding interactions that could serve as a guide for engineering the half-life of antibody Fc fragments. These engineered monomeric Fc molecules also enabled the generation of a novel monovalent bispecific molecular design, which translated the FcRn binding enhancement to improvement of in vivo serum half-life.
Identifiants
pubmed: 34497355
doi: 10.1038/s42003-021-02565-5
pii: 10.1038/s42003-021-02565-5
pmc: PMC8426389
doi:
Substances chimiques
Histocompatibility Antigens Class I
0
Immunoglobulin Fc Fragments
0
Receptors, Fc
0
Fc receptor, neonatal
TW3XAW0RCY
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1048Subventions
Organisme : NIGMS NIH HHS
ID : P41 GM103393
Pays : United States
Informations de copyright
© 2021. The Author(s).
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