AB0482 The cytotoxic effects of certolizumab pegol and golimumab mediated by transmembrane tumor necrosis factor

Background Anti-tumor necrosis factor α (anti-TNFα) agents have been successfully applied for the treatment of rheumatoid arthritis (RA), Crohn’s disease (CD) and other chronic inflammatory diseases. Not only the neutralization of soluble TNFα but also the effect on transmembrane TNFα is important mechanisms of action of anti-TNFα agents. Objectives This study investigated the cytotoxic effects of new anti-TNFα agents, certolizumab pegol and golimumab, that are mediated by transmembrane TNFα. Methods Transmembrane TNFα-expressing Jurkat T cells that did not express TNF receptors were used. The binding ability of each anti-TNFα agent to transmembrane TNFα, antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and the apoptotic effect were examined. Results Certolizumab pegol and golimumab bound to transmembrane TNFα. Golimumab induced ADCC and CDC, which was comparable to infliximab and adalimumab. However, certolizumab pegol did not induce ADCC or CDC. Certolizumab pegol directly induced nonapoptotic cell death in transmembrane TNFα-expressing cells. Golimumab induced a weaker apoptotic effect than infliximab and adalimumab. Conclusions The cytotoxic effects of anti-TNFα agents on TNFα-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 TNFα-producing cells may contribute to its clinical efficacy in CD. Golimumab may be less effective for granulomatous diseases. Disclosure of Interest None Declared