Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Differences in promiscuity for antibody-FcRn interactions across species: implications for therapeutic antibodies
Autore:
Ober, RJ; Radu, CG; Ghetie, V; Ward, ES;
Indirizzi:
Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75390 USA Univ Texas Dallas TX USA 75390 Ctr Canc Immunobiol, Dallas, TX 75390 USA Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75390 USA Univ Texas Dallas TX USA 75390 Med Ctr, Ctr Immunol, Dallas, TX 75390 USA
Titolo Testata:
INTERNATIONAL IMMUNOLOGY
fascicolo: 12, volume: 13, anno: 2001,
pagine: 1551 - 1559
SICI:
0953-8178(200112)13:12<1551:DIPFAI>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
I-RELATED RECEPTOR; CRYSTAL-STRUCTURE; IMMUNOGLOBULIN-G; HUMAN PLACENTA; BIDIRECTIONAL TRANSCYTOSIS; MONOCLONAL-ANTIBODIES; 2.8-A RESOLUTION; MURINE IGG1; PROTEIN-A; COMPLEX;
Keywords:
antibody; FcRn; interactions; promiscuity; therapeutic antibodies;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Ward, ES Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, 6000 Harry Hines Blvd, Dallas, TX 75390 USA Univ Texas 6000 Harry Hines Blvd Dallas TX USA 75390 TX 75390 USA
Citazione:
R.J. Ober et al., "Differences in promiscuity for antibody-FcRn interactions across species: implications for therapeutic antibodies", INT IMMUNOL, 13(12), 2001, pp. 1551-1559

Abstract

Preclinical tests of therapeutic antibodies are frequently carried out in mice to evaluate pharmacokinetics and efficacy. However, the observation that mouse IgG are cleared rapidly from the human circulation suggests that mice may not always be an ideal model. The Fc receptor, FcRn, regulates the serum half-lives of IgG in mice and most likely has a similar function in humans. In the current study we have carried out an extensive analysis of the interaction of the human or mouse forms of FcRn with IgG from various species using surface plasmon resonance. We show that in contrast to mouse FcRn, human FcRn is surprisingly stringent in its binding specificity for IgG derived from different species. Human FcRn binds to human, rabbit and guinea pig IgG, but not significantly to rat, bovine, sheep or mouse IgG (with the exception of weak binding to mouse IgG2b). In contrast, mouse FcRn bindsto all IgG analyzed. The lack of binding of human FcRn to mouse IgG1 has been confirmed using transfectants that have been engineered to express human FcRn on the cell surface. Our results provide a molecular explanation forthe enigmatic observation that mouse IgG behave anomalously in humans. These studies have implications for the successful application of therapeutic antibodies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/10/20 alle ore 02:57:34