Complement-mediated tumor-specific cell lysis by antibody combinations targeting epidermal growth factor receptor (EGFR) and its variant III (EGFRvIII)
作者： Katja Klausz , Sven Berger , Jeroen J. Lammerts van Bueren , Stefanie Derer , Stefan Lohse
DOI: 10.1111/J.1349-7006.2011.02019.X
关键词:
摘要: Monoclonal antibodies (mAb) against variant III of epidermal growth factor receptor (EGFRvIII) hold promise for improving tumor selectivity EGFR-targeted therapy. Here, we compared Fc-mediated effector functions three mAb EGFRvIII (MR1-1, ch806, 13.1.2) with those zalutumumab, a high affinity EGFR in advanced clinical trials. MR1-1 and ch806 demonstrated preferential 13.1.2 exclusive binding to EGFRvIII, contrast which bound both wild-type EGFRvIII. All four human IgG1κ mediated antibody-dependent cellular cytotoxicity (ADCC) EGFRvIII-expressing cells mononuclear isolated monocytes, while only zalutumumab addition triggered ADCC by polymorphonuclear cells. Interestingly, combinations specifically complement-dependent (CDC) EGFRvIII-transfected but not Moreover, EGFRvIII-specific CDC was significantly enhanced when combined Fc-engineered (K326A/E333A). These observations confirm the immunotherapeutic potential antibody EGFR, demonstrate that can be improved combining therapeutic an
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