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Titolo:
INCREASING THE SERUM PERSISTENCE OF AN IGG FRAGMENT BY RANDOM MUTAGENESIS
Autore:
GHETIE V; POPOV S; BORVAK J; RADU C; MATESOI D; MEDESAN C; OBER RJ; WARD ES;
Indirizzi:
UNIV TEXAS,SW MED CTR,DEPT MICROBIOL,5323 HARRY HINES BLVD DALLAS TX 75235 UNIV TEXAS,SW MED CTR,DEPT MICROBIOL DALLAS TX 75235 UNIV TEXAS,SW MED CTR,CTR CANC IMMUNOBIOL DALLAS TX 75235
Titolo Testata:
Nature biotechnology
fascicolo: 7, volume: 15, anno: 1997,
pagine: 637 - 640
SICI:
1087-0156(1997)15:7<637:ITSPOA>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEONATAL FC RECEPTOR; IMMUNOGLOBULIN-G; ESCHERICHIA-COLI; BINDING-SITE; ANTIBODY; RAT; LOCALIZATION; PROTEINS; COMPLEX; FETAL;
Keywords:
ANTIBODY ENGINEERING; PHARMACOKINETICS; PHAGE DISPLAY; SURFACE PLASMON RESONANCE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
33
Recensione:
Indirizzi per estratti:
Citazione:
V. Ghetie et al., "INCREASING THE SERUM PERSISTENCE OF AN IGG FRAGMENT BY RANDOM MUTAGENESIS", Nature biotechnology, 15(7), 1997, pp. 637-640

Abstract

The major histocompatibility complex (MHC) class I-related receptor FcRn is involved in regulating serum gammaglobulin (IgG) levels in mice. With the aim of increasing the serum half-life of a recombinant murine Fc gamma 1 fragment, the affinity far binding to FcRn at pH 6.0 hasbeen increased by random mutagenesis of Thr252, Thr254, and Thr256 followed by selection using bacteriophage display. These residues were chosen as they are in proximity to the FcRn-IgG (Fc) interaction site. Two mutants with higher affinity (due to lower off-rates) than the wild-type Fc have been isolated and analyzed in pharmacokinetic studies in mice. The mutant with the highest affinity has a significantly longer serum half-life than the wild type fragment, despite its lower off-rate from FcRn at pH 7.4. The results provide support for the involvement of FcRn in the homeostasis of serum IgGs in mice. The indications that a homologous FcRn regulates IgG levels in humans suggest that thisapproach has implications for increasing the serum persistence of therapeutic antibodies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 22:16:17