Binding and functional comparisons of two types of tumor necrosis factor antagonists.

  title={Binding and functional comparisons of two types of tumor necrosis factor antagonists.},
  author={Bernard J. Scallon and Ann Cai and Nancy L Solowski and Amy S. Rosenberg and Xiao-yu Song and David J Shealy and Carrie L. Wagner},
  journal={The Journal of pharmacology and experimental therapeutics},
  volume={301 2},
  • B. ScallonAnn Cai C. Wagner
  • Published 1 May 2002
  • Biology, Medicine
  • The Journal of pharmacology and experimental therapeutics
Two tumor necrosis factor (TNF) antagonists infliximab (a chimeric monoclonal antibody) and etanercept (a p75 TNF receptor/Fc fusion protein) have been approved for treatment of rheumatoid arthritis. However, these agents have shown different degrees of clinical benefit in controlled clinical trials in other TNF-mediated diseases such as Crohn's disease (CD) and psoriasis. We investigated whether structural differences between these two antagonists translate into different binding and… 

Figures and Tables from this paper

Binding characteristics of tumor necrosis factor receptor-Fc fusion proteins vs anti-tumor necrosis factor mAbs.

The absence of large complex formation with the binding of soluble receptor-fusion proteins to TNF may account for the different clinical efficacy and safety profiles of the two classes of TNF antagonists.

Inhibitors of tumor necrosis factor-a and mechanisms of their action

Although TNF-α inhibitors are present in clinical practice for more than two decades and are established as an efficacious therapeutics, researchers are still occupied by revealing the complex mechanisms of their action.

Pharmacology of TNF blockade in rheumatoid arthritis and other chronic inflammatory diseases.

  • P. Taylor
  • Biology
    Current opinion in pharmacology
  • 2010

[Differences in pharmacology of tumor necrosis factor (TNF) antagonists].

The dynamics of interaction of the two classes of neutralizing molecules with TNF, and the ability in restoring TNF homeostasis, are outlined.

Infliximab: how to use it in pediatric Crohn's disease.

  • F. Ruemmele
  • Medicine, Biology
    Journal of pediatric gastroenterology and nutrition
  • 2004
The efficacy of infliximab in adult patients with fistulizing CD is well demonstrated, with an efficacy of greater than 65% with a remission rate of 40% to 50% for active luminal CD after a single infusion (6).

Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-alpha.

The mTNF motifs and the downstream intracellular molecular events essential for reverse signaling through transmembrane TNF-alpha are revealed and will provide insight into the novel role of mT NF in inflammation.

Molecular differences in anticytokine therapies.

  • L. Calabrese
  • Biology
    Clinical and experimental rheumatology
  • 2003
The molecular characteristics of these agents may be relevant to clinical efficacy and safety and additional long-term data will be required to determine the relative benefits and drawbacks of different molecular characteristics in these anticytokine agents.



Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein.

In this three-month trial TNFR:Fc was safe, well tolerated, and associated with improvement in the inflammatory symptoms of rheumatoid arthritis.

Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists.

Results indicate that dimeric sTNFR are effective inhibitors of TNF and under some circumstances function simultaneously as both TNF "carriers" and antagonists of T NF biologic activity.

Chimeric anti-TNF-α monoclonal antibody cA2 binds recombinant transmembrane TNF-α and activates immune effector functions

Findings indicate that, in addition to blocking soluble TNF-α activity, cA2 can bind to transmembrane T NF-α in vitro and suggest that cA 2 binding may lead to lysis of TNF -α-expressing cells in vivo.

The mouse/human chimeric monoclonal antibody cA2 neutralizes TNF in vitro and protects transgenic mice from cachexia and TNF lethality in vivo.

Results demonstrated that cA2 effectively neutralized a broad range of TNF biological activities both in vitro and in vivo.

Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions.

Findings indicate that, in addition to blocking soluble TNF-alpha activity, cA2 can bind to transmembrane T NF-alpha in vitro and suggest that cA1 binding may lead to lysis of TNF -alpha-expressing cells in vivo.

Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis.

The capacity of the antibody to reduce the clinical score, paw swelling, and the histological severity of disease even when injected after the onset of clinical arthritis was found, which has implications for possible modes of therapy of human arthritis.

Construction and initial characterization of a mouse-human chimeric anti-TNF antibody.

Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent

Infliximab is a humanized antibody against tumor necrosis factor α (TNF-α) that is used in the treatment of Crohn's disease and rheumatoid arthritis but there is no direct evidence of a protective role of TNF- α in patients with tuberculosis.

A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate.

In patients with persistently active rheumatoid arthritis, the combination of etanercept and methotrexate was safe and well tolerated and provided significantly greater clinical benefit than metotrexate alone.