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Titolo:
Development of a novel, nonimmunogenic, soluble human TNF receptor type I (sTNFR-I) construct in the baboon
Autore:
Rosenberg, JJ; Martin, SW; Seely, JE; Kinstler, O; Gaines, GC; Fukuzuka, K; Rose, J; Kohno, T; Boyle, WJ; Nelson, A; Kieft, GL; Marshall, WS; Feige, U; Gasser, J; St Clair, J; Frazier, J; Abouhamze, A; Moldawer, LL; Edwards, CK;
Indirizzi:
Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32610 USA Univ FloridaGainesville FL USA 32610 ept Surg, Gainesville, FL 32610 USA Amgen Colorado, Boulder, CO 80301 USA Amgen Colorado Boulder CO USA 80301Amgen Colorado, Boulder, CO 80301 USA Amgen Inc, Thousand Oaks, CA 91320 USA Amgen Inc Thousand Oaks CA USA 91320 gen Inc, Thousand Oaks, CA 91320 USA
Titolo Testata:
JOURNAL OF APPLIED PHYSIOLOGY
fascicolo: 5, volume: 91, anno: 2001,
pagine: 2213 - 2223
SICI:
8750-7587(2001)91:5<2213:DOANNS>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
NECROSIS-FACTOR RECEPTOR; FUSION PROTEIN; RHEUMATOID-ARTHRITIS; SEPTIC SHOCK; MONOCLONAL-ANTIBODY; FACTOR-ALPHA; EFFICACY; IMMUNOADHESIN; PROTECTION; INHIBITOR;
Keywords:
immunoadhesin; sepsis; pharmacokinetics; inflammation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Moldawer, LL Univ Florida, Coll Med, Dept Surg, POB 100286, Gainesville, FL 32610 USA Univ Florida POB 100286 Gainesville FL USA 32610 FL 32610 USA
Citazione:
J.J. Rosenberg et al., "Development of a novel, nonimmunogenic, soluble human TNF receptor type I (sTNFR-I) construct in the baboon", J APP PHYSL, 91(5), 2001, pp. 2213-2223

Abstract

Pharmacokinetics and immunogenicity of six different recombinant human soluble p55 tumor necrosis factor (TNF) receptor I (sTNFR-I) constructs were evaluated in juvenile baboons. The constructs included either an sTNFR-I IgG1 immunoadhesin (p55 sTNFR-I Fc) or five different sTNFR-I constructs covalently linked to polyethylene glycol. The constructs were administered intravenously three times, and pharmacokinetics and immunogenicity were examinedover 63 days. All of the constructs were immunogenic, with the exception of a 2.6-domain monomeric sTNFR-I. To evaluate whether the nonimmunogenic 2.6-domain monomeric construct could protect baboons against TNF-alpha -induced mortality, baboons were pretreated with 1, 5, or 10 mg/kg body wt and were compared with baboons receiving either placebo or 1 mg/kg body wt of thedimeric 4.0-domain sTNFR-I construct (n = 3 each) before lethal Escherichia coli bacteremia. The monomeric construct protected baboons and neutralized TNF bioactivity, although greater quantities were required compared with the dimeric 4.0-domain sTNFR-I construct. We conclude that E. coli-recombinant-derived human sTNFR-I constructs can be generated with minimal immunogenicity on repeated administration and still protect against the consequences of exaggerated TNF-alpha production.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 21:25:05