Human IgG2 Antibodies against Epidermal Growth Factor Receptor Effectively Trigger Antibody-Dependent Cellular Cytotoxicity but, in Contrast to IgG1, Only by Cells of Myeloid Lineage

摘要: Ab-dependent cellular cytotoxicity (ADCC) is usually considered an important mechanism of action for immunotherapy with human IgG1 but not IgG2 Abs. The epidermal growth factor receptor (EGF-R) Ab panitumumab represents the only approved and inhibition EGF-R signaling has been described as its principal action. In this study, we investigated effector mechanisms compared zalutumumab, isotype. Notably, was effective zalutumumab in recruiting ADCC by myeloid cells (i.e., neutrophils monocytes) contrast to NK cell-mediated ADCC, which induced Ab. Neutrophil-mediated tumor cell killing could be stimulated factors triggered via FcgammaRIIa. Panitumumab-mediated significantly affected functional FcgammaRIIa-R131H polymorphism more effectively from FcgammaRIIa-131H homozygous donors than -131R individuals. This did affect neutrophil zalutumumab. vivo activity both Abs assessed two animal models: a high-dose model, dominant action, low-dose recruitment plays prominent role. Zalutumumab reflecting stronger ability induce downmodulation inhibition. similarly prevented growth. Thus, our results identify potent additional EGF-R-directed immunotherapy.