Mechanisms of G-CSF- or GM-CSF-stimulated tumor cell killing by Fc receptor-directed bispecific antibodies
Stockmeyer, Bernhard, Elsässer, David, Dechant, Michael, Repp, Roland, Gramatzki, Martin, Glennie, Martin J., van de Winkel, Jan G.J. and Valerius, Thomas (2001) Mechanisms of G-CSF- or GM-CSF-stimulated tumor cell killing by Fc receptor-directed bispecific antibodies. Journal of Immunological Methods, 248, (1-2), 103-111. (doi:10.1016/S0022-1759(00)00346-X).
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Studies with gene-modified mice have recently reinforced the importance of Fc receptor-mediated effector mechanisms for the therapeutic efficacy of rituxan and herceptin — two clinically approved antibodies for the treatment of tumor patients. We investigated Fc receptor-dependent tumor cell killing by mononuclear and granulocytic effector cells — comparing human IgG1 antibodies against CD20 or HER-2/neu with their respective FcγRI (CD64)-, FcγRIII (CD16)-, or FcαRI (CD89)-directed bispecific derivatives. With blood from healthy donors as effector source, human IgG1 and FcγRIII (CD16)-directed bispecific antibodies proved most effective in recruiting mononuclear effector cells, whereas tumor cell killing by granulocytes was most potently triggered by FcαRI-directed bispecific constructs. Granulocyte-mediated tumor cell lysis was significantly enhanced when blood from G-CSF- or GM-CSF-treated patients was investigated. Interestingly, however, both myeloid growth factors improved effector cell recruitment by different mechanisms, which were furthermore dependent on the tumor target antigen, and on the selected cytotoxic Fc receptor.
|Digital Object Identifier (DOI):||doi:10.1016/S0022-1759(00)00346-X|
|Keywords:||antibody therapy, bispecific antibody, colony-stimulating factors, granulocytes, fc receptors|
|Subjects:||R Medicine > R Medicine (General)
Q Science > QH Natural history > QH301 Biology
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Cancer Sciences
|Date Deposited:||20 Apr 2006|
|Last Modified:||06 Aug 2015 02:27|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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