Infliximab chimeric antitumor necrosis factor-a monoclonal antibody as potential treatment for myelodysplastic syndromes

Leuk Lymphoma. 2005 Apr;46(4):509-16. doi: 10.1080/10428190400027829.

Abstract

Accumulating evidence indicates tumor necrosis factor-a (TNF-a) as a key cytokine in the pathogenesis of the myelodysplastic syndromes (MDS). The identification of TNF-a as a regulator of apoptosis and the increased susceptibility of MDS cells to this cytokine provided the basis for several clinical trials of TNF inhibitors. Infliximab is an IgG1 chimeric anti-TNF-a monoclonal antibody composed of human constant and murine variable regions that bind specifically to both soluble and membrane-bound TNF-a. To date, only 2 studies have investigated the use of infliximab in patients with low-risk MDS. In both reports the drug showed a limited but significant activity and a favorable side-effect profile. In some patients, hematopoietic response was associated with decreased apoptosis as well as a decrease in abnormal metaphases by 50%. Further studies are currently underway and should provide useful information to define the more responsive subtypes of MDS, the patient characteristics, and the proper dosing regimen.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Humans
  • Infliximab
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha
  • Infliximab