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- W2342253365 abstract "11055 Targeted therapy against the epidermal growth factor receptor (EGF-R) has been introduced into clinical practice for several solid tumors. Thus far, EGF-R- directed antibodies have received approval for the treatment of advanced colorectal and head and neck cancer. Recent studies demonstrated an association between Fcg receptor polymorphisms and clinical outcome. Here, we investigated effector mechanisms of the human IgG2 antibody pantitumumab and zalutumumab—a human IgG1 antibody against EGF-R, currently in phase III clinical evaluation. Both antibodies had similar binding characteristics, but differed in induction of antibody- dependent cellular cytotoxicity (ADCC). Zalutumumab induced potent MNC-mediated ADCC via FcgRIII (CD16), which was poorly triggered by panitumumab. Interestingly, not only zalutumumab but also panitumumab recruited neutrophils for ADCC. Neutrophil- mediated killing is triggered via FcgRIIa (CD32), and is potentially affected by its 131R/H polymorphism. Thus, panitumumab- mediated ADCC was more effective by neutrophils from FcgRIIa-131H homozygous individuals than from -131R individuals. ADCC induced by the IgG1 antibody zalutumumab was not affected by this polymorphism. In an experimental metastasis model in mice, both zalutumumab and panitumumab prevented establishment of metastases at low antibody concentrations which allowed the induction of ADCC but not the inhibition of signalling. Our results may implicate neutrophil- mediated ADCC in the in vivo mechanisms of action of EGF-R- directed antibodies, and suggest that heterogeneity in clinical responses due to the FcgRIIa-131R/H polymorphism can be expected for panitumumab. [Table: see text]" @default.
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- W2342253365 date "2009-05-20" @default.
- W2342253365 modified "2023-10-12" @default.
- W2342253365 title "Effect of the epidermal growth factor receptor antibody panitumumab on triggering of ADCC" @default.
- W2342253365 doi "https://doi.org/10.1200/jco.2009.27.15_suppl.11055" @default.
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