The Cytotoxic Effects of Certolizumab Pegol and Golimumab Mediated by Transmembrane Tumor Necrosis Factor α

Background:Anti-tumor necrosis factor (anti-TNF-) 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- but also the effect on transmembrane TNF- is important mechanisms of action of anti-TNF- agents. This study investigated the cytotoxic effects of new anti-TNF- agents, certolizumab pegol and golimumab, which are mediated by transmembrane TNF-.Methods:Transmembrane TNF--expressing Jurkat T cells that did not express TNF receptors were used. The binding ability of each anti-TNF- agent to transmembrane TNF-, antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and the apoptotic effect were examined.Results:Certolizumab pegol and golimumab bound to transmembrane TNF-. 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--expressing cells. Golimumab induced a weaker apoptotic effect than infliximab and adalimumab.Conclusions:The cytotoxic effects of anti-TNF- agents on TNF--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--producing cells may contribute to its clinical efficacy in Crohn's disease. Golimumab may be less effective for granulomatous diseases.