The cytotoxic effects of certolizumab pegol and golimumab mediated by transmembrane tumor necrosis factor α.
Inflamm Bowel Dis
; 19(6): 1224-31, 2013 May.
Article
em En
| MEDLINE
| ID: mdl-23619715
ABSTRACT
BACKGROUND:
Anti-tumor necrosis factor α (anti-TNF-α) agents have been successfully applied for the treatment of rheumatoid arthritis, Crohn's disease, and other chronic inflammatory diseases. Not only the neutralization of soluble TNF-α but also the effect on transmembrane TNF-α is important mechanisms of action of anti-TNF-α agents. This study investigated the cytotoxic effects of new anti-TNF-α agents, certolizumab pegol and golimumab, which are mediated by transmembrane TNF-α.METHODS:
Transmembrane TNF-α-expressing Jurkat T cells that did not express TNF receptors were used. The binding ability of each anti-TNF-α agent to transmembrane TNF-α, antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and the apoptotic effect were examined.RESULTS:
Certolizumab pegol and golimumab bound to transmembrane TNF-α. Golimumab induced antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, which was comparable to infliximab and adalimumab. However, certolizumab pegol did not induce antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity. Certolizumab pegol directly induced nonapoptotic cell death in transmembrane TNF-α-expressing cells. Golimumab induced a weaker apoptotic effect than infliximab and adalimumab.CONCLUSIONS:
The cytotoxic effects of anti-TNF-α agents on TNF-α-expressing cells are considered to be associated with the clinical effect of these agents on granulomatous diseases. The direct cytotoxic effect of certolizumab pegol on TNF-α-producing cells may contribute to its clinical efficacy in Crohn's disease. Golimumab may be less effective for granulomatous diseases.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polietilenoglicóis
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Fragmentos Fab das Imunoglobulinas
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Membrana Celular
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Fator de Necrose Tumoral alfa
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Apoptose
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Proliferação de Células
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Anticorpos Monoclonais Humanizados
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Imunossupressores
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Anticorpos Monoclonais
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article