Molecular mechanisms of action of anti-TNF-α agents – Comparison among therapeutic TNF-α antagonists

Hiroki Mitoma, Takahiko Horiuchi, Hiroshi Tsukamoto, Naoyasu Ueda

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Tumor necrosis factor (TNF)-α is a potent pro-inflammatory and pathological cytokines in inflammatory diseases such as rheumatoid arthritis and inflammatory bowel diseases. Anti-TNF-α therapy has been established as an efficacious therapeutic strategy in these diseases. In clinical settings, three monoclonal anti-TNF-α full IgG1 antibodies infliximab, adalimumab, and golimumab, PEGylated Fab’ fragment of anti-TNF-α antibody certolizumab pegol, extracellular domain of TNF receptor 2/IgG1-Fc fusion protein etanercept, are almost equally effective for rheumatoid arthritis. Although monoclonal full IgG1 antibodies are able to induce clinical and endoscopic remission in inflammatory bowel diseases, certolizumab pegol without Fc portion has been shown to be less effective for inflammatory bowel diseases compared to full IgG1 antibodies. In addition, there are no evidences that etanercept leads clinical remission in inflammatory bowel diseases. Besides the common effect of anti-TNF-α agents on neutralization of soluble TNF-α, each anti-TNF-α agent has its own distinctive pharmacological properties which cause the difference in clinical efficacies. Here we focus on the distinctions of action of anti-TNF-α agents especially in following points; (1) blocking ability against ligands, transmembrane TNF-α and lymphotoxin, (2) effects toward transmembrane TNF-α-expressing cells, (3) effects toward Fcγ receptor-expressing cells, (4) degradation and distribution in inflamed tissue. Accumulating evidence will give us the idea how to modify anti-TNF-α agents to enhance the clinical efficacy in inflammatory diseases.

Original languageEnglish
Pages (from-to)56-63
Number of pages8
JournalCytokine
Volume101
DOIs
Publication statusPublished - Jan 1 2018

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Tumor Necrosis Factor-alpha
Inflammatory Bowel Diseases
Immunoglobulin G
Therapeutics
Antibodies
Rheumatoid Arthritis
Receptors, Tumor Necrosis Factor, Type II
Lymphotoxin-alpha
Immunoglobulin Fab Fragments
Fc Receptors
Fusion reactions
Pharmacology
Tissue
Cytokines
Ligands
Degradation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

Cite this

Molecular mechanisms of action of anti-TNF-α agents – Comparison among therapeutic TNF-α antagonists. / Mitoma, Hiroki; Horiuchi, Takahiko; Tsukamoto, Hiroshi; Ueda, Naoyasu.

In: Cytokine, Vol. 101, 01.01.2018, p. 56-63.

Research output: Contribution to journalArticle

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