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Antibody‐dependent cellular cytotoxicity of cetuximab against tumor cells with wild‐type or mutant epidermal growth factor receptor
Author(s) -
Kimura Hideharu,
Sakai Kazuko,
Arao Tokuzo,
Shimoyama Tatsu,
Tamura Tomohide,
Nishio Kazuto
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00510.x
Subject(s) - antibody dependent cell mediated cytotoxicity , cetuximab , epidermal growth factor receptor , cancer research , cytolysis , cell culture , monoclonal antibody , cytotoxicity , transfection , growth factor receptor , biology , microbiology and biotechnology , antibody , receptor , chemistry , immunology , in vitro , biochemistry , genetics
Cetuximab (Erbitux, IMC‐C225) is a monoclonal antibody targeted to the epidermal growth factor receptor (EGFR). To clarify the mode of antitumor action of cetuximab, we examined antibody‐dependent cellular cytotoxicity (ADCC) activity against several tumor cell lines expressing wild‐type or mutant EGFR. ADCC activity and complement‐dependent cytolysis activity were analyzed using the CytoTox 96 assay. ADCC activities correlated with the EGFR expression value ( R =  0.924). ADCC activities were detected against all tumor cell lines, except K562 cells in a manner dependent on the cellular EGFR expression level, whereas complement‐dependent cytolysis activity was not detected in any of the cell lines. The ADCC activity mediated by cetuximab was examined in HEK293 cells transfected with wild‐type EGFR (293W) and a deletional mutant of EGFR (293D) in comparison with the mock transfectant (293M). ADCC activity was detected in 293W and 293D cells, in a cetuximab dose‐dependent manner, but not in 293M cells (<10%). These results indicate that ADCC‐dependent antitumor activity results from the degree of affinity of cetuximab for the extracellular domain of EGFR, independent of EGFR mutation status. These results suggest ADCC activity to be one of the modes of therapeutic action of cetuximab and to depend on EGFR expression on the tumor cell surface. ( Cancer Sci 2007; 98: 1275–1280)

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