Effects of the CD33-targeted drug gemtuzumab ozogamicin (Mylotarg) on growth and mediator secretion in human mast cells and blood basophils.
OBJECTIVE
Mylotarg (gemtuzumab ozogamicin [GO]) has recently been introduced as a novel CD33-targeting drug in clinical hematology. However, despite efficacy, GO produces significant side effects including an infusion syndrome. We have recently shown that mast cells (MCs) and basophils (BAs) express CD33. In the present study, we investigated the effects of GO on growth and mediator secretion in MCs and BAs.


METHODS
Growth-inhibitory effects of GO on neoplastic MCs (HMC-1) and BAs (KU812) as well as cord blood-derived MC and BA progenitor cells were determined by counting cell numbers and the numbers of apoptotic cells. The amount of histamine secreted from primary MCs and BAs was measured by radioimmunoassay after incubation of cells with GO alone or GO together with an anti-immunoglobulin E (IgE) antibody.


RESULTS
MCs and BAs as well as HMC-1 cells and KU812 cells were found to express CD33 mRNA and the CD33 protein. GO was found to inhibit the growth of HMC-1 cells and KU812 cells as well as stem cell factor-dependent differentiation of MCs and interleukin-3-induced growth of BAs from their cord blood-derived progenitors. The GO-induced inhibition of growth of neoplastic cells was found to be associated with induction of apoptosis. GO neither induced secretion of histamine from MCs or BAs nor upregulated the anti-IgE-induced release of histamine in these cells.


CONCLUSIONS
GO counteracts growth of normal and neoplastic MCs and BAs without inducing rapid release of histamine. The exact value of GO as a targeted drug for the treatment of high-grade MC or BA neoplasms remains to be determined.
Krauth
Maria-Theresa
MT
Department of Internal Medicine I, Division of Hematology & Hemostaseology, Vienna, Austria.
Böhm
Alexandra
A
Agis
Hermine
H
Sonneck
Karoline
K
Samorapoompichit
Puchit
P
Florian
Stefan
S
Sotlar
Karl
K
Valent
Peter
P
D000617:Aminoglycosides / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D001491:Basophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001773:Blood Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology; D000079982:Gemtuzumab; D006632:Histamine / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D063268:Sialic Acid Binding Ig-like Lectin 3; D013234:Stem Cells
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; D006632:Histamine; D000079982:Gemtuzumab