Definition

A pegylated, human, engineered dominant-negative tumor necrosis factor (TNF; TNF-alpha) variant devoid of TNF receptor-binding activity, with potential anti-inflammatory activity. Upon administration, pegipanermin forms heterotrimers with native soluble TNF (sTNF) but not membrane-bound transmembrane TNF (tmTNF). This prevents the binding of sTNF with TNF receptors and inhibits sTNF pro-inflammatory signaling, thereby reducing inflammation. TNF, a pro-inflammatory cytokine, is upregulated in various diseases and in cytokine storm. sTNF signaling, primarily via TNF receptor 1 (TNFR1; CD120a; p55/p60), may be responsible for exacerbation of existing inflammatory response while tmTNF signaling, primarily via TNF receptor 2 (TNFR2; CD120b; p75/p80), plays an important role in immune system development and cell survival.