Direct effect of bispecific anti-CD33 x anti-CD64 antibody on proliferation and signaling in myeloid cells.
Bispecific anti-CD33 x anti-CD64 antibody (BsAb) directly inhibited proliferation and colony formation of human acute myeloid leukemia cell lines, without affecting the function of normal monocytes. Addition of BsAb to normal monocytes induced tyrosine phosphorylation of Cbl and Vav, association of these molecules with CD33, and downstream signaling. In leukemia cells that were insensitive to BsAb treatment, Vav and Cbl were constitutively phosphorylated and, therefore, constitutively associated with CD33. Direct growth inhibition is an additional mechanism by which BsAb may be useful in the therapy of AML.
Balaian
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Department of Medicine and Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA 92093-0960, USA.
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D018033:Antibodies, Bispecific / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology* / Q000502:physiology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology* / Q000502:physiology; D002455:Cell Division; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D009000:Monocytes / Q000276:immunology; D010587:Phagocytosis; D010766:Phosphorylation; D017452:Receptors, IgG / Q000276:immunology* / Q000502:physiology; D063268:Sialic Acid Binding Ig-like Lectin 3; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
D018033:Antibodies, Bispecific; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D017452:Receptors, IgG; D063268:Sialic Acid Binding Ig-like Lectin 3; C076715:pervanadate; D014638:Vanadates; D014443:Tyrosine; D007371:Interferon-gamma