Differences in binding and effector functions between classes of TNF antagonists.
Article Details
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Arora T, Padaki R, Liu L, Hamburger AE, Ellison AR, Stevens SR, Louie JS, Kohno T
Differences in binding and effector functions between classes of TNF antagonists.
Cytokine. 2009 Feb;45(2):124-31. doi: 10.1016/j.cyto.2008.11.008. Epub 2009 Jan 6.
- PubMed ID
- 19128982 [ View in PubMed]
- Abstract
There are currently two Food and Drug Administration-approved classes of biologic agents that target tumor necrosis factor-alpha (TNF-alpha): anti-TNF monoclonal antibodies (mAbs) (adalimumab and infliximab), and soluble TNF receptors (etanercept). This study examined the ability of the TNF antagonists to: (1) bind various polymorphic variants of cell surface-expressed Fc receptors (FcgammaRs) and the complement component C1q, and (2) mediate Ab-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC) killing of cells expressing membrane-bound TNF (mTNF) in vitro. Both mAbs and the soluble TNF receptor demonstrated low-level binding to the activating receptors FcgammaRI, FcgammaRIIa, and FcgammaRIIIa, and the inhibitory receptor FcgammaRIIb, in the absence of exogenous TNF. However, upon addition of TNF, the mAbs, but not etanercept, showed significantly increased binding, in particular to the FcgammaRII and FcgammaRIII receptors. Infliximab and adalimumab induced ADCC much more potently than etanercept. In the presence of TNF, both mAbs bound C1q in in vitro assays, but etanercept did not bind C1q under any conditions. Infliximab and adalimumab also induced CDC in cells expressing mTNF more potently than etanercept. Differences in the ability to bind ligand and mediate cell death may account for the differences in efficacy and safety of TNF antagonists.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Etanercept High affinity immunoglobulin gamma Fc receptor I Protein Humans UnknownLigandDetails Etanercept Low affinity immunoglobulin gamma Fc region receptor II-a Protein Humans UnknownLigandDetails Etanercept Low affinity immunoglobulin gamma Fc region receptor II-b Protein Humans UnknownLigandDetails Etanercept Low affinity immunoglobulin gamma Fc region receptor II-c Protein Humans UnknownLigandDetails Etanercept Low affinity immunoglobulin gamma Fc region receptor III-A Protein Humans UnknownLigandDetails Etanercept Low affinity immunoglobulin gamma Fc region receptor III-B Protein Humans UnknownLigandDetails