Infliximab chimeric antitumor necrosis factor-a monoclonal antibody as potential treatment for myelodysplastic syndromes.
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.
Stasi
Roberto
R
Department of Medical Sciences, Regina Apostolorum Hospital, Albano Laziale, Italy. roberto.stasi@uniroma2.it
Amadori
Sergio
S
Newland
Adrian C
AC
Provan
Drew
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D006801:Humans; D000069285:Infliximab; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab