Binding and Functional Comparisons of Two Types of Tumor Necrosis Factor Antagonists

Scallon, Bernie; Cai, Ann; Solowski, Nancy; Rosenberg, Amy S.; Song, Xiaoyu; Shealy, David J.; Wagner, Carrie

doi:10.1124/jpet.301.2.418

Cited by 606 publications

(491 citation statements)

References 36 publications

Supporting

Mentioning

444

Contrasting

Unclassified

Order By: Relevance

“…Infliximab, by virtue of being IgGI antibodies, can activate complement and bind Fc receptor and it also can bind both monomeric and trimeric solTNF and tmTNF, whereas etanercept only binds TNF trimers and interacts with tmTNF with reduced avidity, compared with that of infliximab [82,[110][111][112].…”

Section: A C C E P T E D Article In Pressmentioning

confidence: 99%

TNF-α inhibitors in asthma and COPD: We must not throw the baby out with the bath water

Matera

Calzetta

Cazzola

2010

Pulmonary Pharmacology & Therapeutics

117

View full text Add to dashboard Cite

Tumor necrosis factor (TNF)-α, a pleiotropic cytokine that exerts a variety of effects, such as growth promotion, growth inhibition, angiogenesis, cytotoxicity, inflammation, and immunomodulation, has been implicated in several inflammatory conditions. It plays a significant role in many inflammatory diseases of lung. Given that there is significant literature supporting the pathobiologic role of TNF-α in asthma, mainly in severe refractory asthma, and COPD, TNF-α inhibitors (infliximab, golimumab and etanercept) are now regarded as potential new medications in asthma and COPD management. The studies reported in literature indicate that TNF-α inhibitors are effective in a relatively small subgroup of patients with severe asthma, possibly defined by an increased TNF axis, but they seem to be ineffective in COPD, although an observational study demonstrated that TNF-α inhibitors were associated with a reduction in the rate of COPD hospitalisation among patients with COPD receiving these agents to treat their rheumatoid arthritis. These findings require a smart approach because there is still good reason to target TNF-α, perhaps in a more carefully selected patient group. TNF-α treatment should therefore not be thrown out, or abandoned. Indeed, since severe asthma and COPD are heterogeneous diseases that have characteristics that occur with different phenotypes remained poorly characterized and little known about the underlying pathobiology contributing to them, it is likely that definition of these phenotypes and choice of the right outcome measure will allow us to understand which kind of patients can benefit from TNF-α inhibitors.

show abstract

Section: A C C E P T E D Article In Pressmentioning

confidence: 99%

TNF-α inhibitors in asthma and COPD: We must not throw the baby out with the bath water

Matera

Calzetta

Cazzola

2010

Pulmonary Pharmacology & Therapeutics

117

View full text Add to dashboard Cite

show abstract

“…Several of these studies have been performed using cell lines into which a gene encoding non-cleavable mTNF has been transfected. As discussed later in the next subsection, investigators have found differences in various anti-TNF agents in their ability to bind tmTNF [16]. Newer data suggest that the cross-linking of anti-TNF Ab on the cell is responsible for its reverse intracellular signaling, inhibiting the production of inflammatory cytokines, inducing apoptosis, and causing growth arrest.…”

Section: Intracellular Signaling Mediated By Anti-tnfα Agentsmentioning

confidence: 99%

“…At first the gene encoding tmTNF was transfected as a deletion mutant, but more recently, Harashima et al [68] developed a method of transfecting cells with a tmTNF rendered non-cleavable by site-directed mutagenesis. Using these methods, investigators assessed the number of anti-TNF molecules that can bind tmTNF either by flow cytometry or by radioassay [16].…”

Section: Limiting Factors Contributing To Disease Restriction In Thermentioning

confidence: 99%

“…INF is able to bind to both monomeric as well as trimeric forms of TNF, but because of its binding site on TNF occurs in the cleft between subunits, ETA can only bind to the trimeric form [16]. This binding configuration may explain why the number of mTNF molecules bound by INF is 1.5 to 3 times as many as ETA, while their affinities in monovalent interactions are similar.…”

Section: Limiting Factors Contributing To Disease Restriction In Thermentioning

confidence: 99%

“…This binding configuration may explain why the number of mTNF molecules bound by INF is 1.5 to 3 times as many as ETA, while their affinities in monovalent interactions are similar. Scallon et al [16] performed pulse-chase experiments of radiolabeled INF and ETA and found that while both bound tmTNF, ETA had a higher off-rate, signifying that the rate of exchange of ETA with tmTNF is higher than that of INF. A recent study from the Abbott Laboratories compared the binding properties of the three FAD-approved anti-TNF agents [69].…”

Section: Limiting Factors Contributing To Disease Restriction In Thermentioning

confidence: 99%

See 2 more Smart Citations

TNFα blockade in human diseases: Mechanisms and future directions

Wong

Ziring

Korin

et al. 2008

Clinical Immunology

255

162

View full text Add to dashboard Cite

Tumor necrosis factor-alpha (TNFα) antagonists have shown remarkable efficacy in a variety of immune-mediated inflammatory diseases (IMIDs). Therapeutic scope and limitations of these agents are reviewed in a recently published article in the Journal. In spite of their therapeutic popularity, little is known about their modes of action in vivo and factors that limit their scope of therapeutic use. Intriguingly, while all TNFα antagonists including blocking antibodies and soluble receptors are effective in certain IMIDs, only anti-TNFα antibodies are effective in other IMIDs. Early efforts at understanding how TNFα antagonists act in IMIDs centered on their ability to neutralize soluble TNFα or to block TNF receptors from binding to their ligands. Subsequent studies suggested a role of complement-mediated lysis or antibody-dependent cell cytotoxicity in their therapeutic effects. More recent models postulate that TNFα blockers may act by affecting intracellular signaling, with the end result being a hastened cell cycle arrest, apoptosis, suppression of cytokine production, or improved Treg cell function. TNFα antagonists can also modulate the functions of myofibroblasts and osteoclasts, which might explain how TNFα antagonists reduce tissue damage in chronic IMIDs. Focusing on the human therapeutic experience, this analytical review will review the biology of mechanisms of action, the limiting factors contributing to disease restriction in therapeutic efficacy, and the mechanism and frequency of treatment-limiting adverse responses of TNFα antagonists. It is hoped that the overview will address the needs of clinicians to decide on optimal use, spur clinical innovation, and incite translational researchers to set priorities for in vivo human investigations.

show abstract

Anti-tumour necrosis factor biological therapies for the treatment of uveitic macular oedema (UMO) for non-infectious uveitis

Barry

Tallouzi

Bucknall

et al. 2017

Cochrane Database of Systematic Reviews

View full text Add to dashboard Cite

Link to publication on Research at Birmingham portal Publisher Rights Statement: Checked for eligibillity 15/01/2019 "This Cochrane Review was published in the Cochrane Database of Systematic Reviews 2018. Issue 12. Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Cochrane Review." Barry et al., Antitumour necrosis factor biological therapies for the treatment of uveitic macular oedema (UMO) for noninfectious uveitis.

show abstract

Binding and Functional Comparisons of Two Types of Tumor Necrosis Factor Antagonists

Abstract: 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 differ-

Cited by 606 publications

References 36 publications

TNF-α inhibitors in asthma and COPD: We must not throw the baby out with the bath water

TNF-α inhibitors in asthma and COPD: We must not throw the baby out with the bath water

TNFα blockade in human diseases: Mechanisms and future directions

Anti-tumour necrosis factor biological therapies for the treatment of uveitic macular oedema (UMO) for non-infectious uveitis

Contact Info

Product

Resources

About