Complement-mediated tumor-specific cell lysis by antibody combinations targeting epidermal growth factor receptor (EGFR) and its variant III (EGFRvIII)
Autor: | Paul W. H. I. Parren, Thomas Valerius, Sven Berger, Jeroen J. Lammerts van Bueren, Katja Klausz, Michael Dechant, Matthias Peipp, Stefanie Derer, Jan G. J. van de Winkel, Stefan Lohse |
---|---|
Rok vydání: | 2011 |
Předmět: |
Cytotoxicity
Immunologic Cancer Research Neutrophils medicine.drug_class CHO Cells Antibodies Monoclonal Humanized Monoclonal antibody Zalutumumab Growth factor receptor Cell Line Tumor Cricetinae medicine Animals Humans Epidermal growth factor receptor Cytotoxicity Antibody-dependent cell-mediated cytotoxicity biology Antibody-Dependent Cell Cytotoxicity Antibodies Monoclonal Complement System Proteins General Medicine ErbB Receptors HEK293 Cells Oncology Monoclonal Immunology Cancer research biology.protein Antibody Epitope Mapping medicine.drug |
Zdroj: | Cancer Science. 102:1761-1768 |
ISSN: | 1347-9032 |
Popis: | Monoclonal antibodies (mAb) against variant III of epidermal growth factor receptor (EGFRvIII) hold promise for improving tumor selectivity of EGFR-targeted therapy. Here, we compared Fc-mediated effector functions of three mAb against EGFRvIII (MR1-1, ch806, 13.1.2) with those of zalutumumab, a high affinity EGFR mAb in advanced clinical trials. MR1-1 and ch806 demonstrated preferential and 13.1.2 exclusive binding to EGFRvIII, in contrast to zalutumumab, which bound both wild-type and EGFRvIII. All four human IgG1κ mAb mediated antibody-dependent cellular cytotoxicity (ADCC) of EGFRvIII-expressing cells with mononuclear cells and isolated monocytes, while only zalutumumab in addition triggered ADCC by polymorphonuclear cells. Interestingly, combinations of zalutumumab and EGFRvIII mAb specifically mediated complement-dependent cytotoxicity (CDC) of EGFRvIII-transfected but not wild-type cells. Moreover, EGFRvIII-specific CDC was significantly enhanced when zalutumumab was combined with a Fc-engineered variant of MR1-1 (K326A/E333A). These observations confirm the immunotherapeutic potential of antibody combinations against EGFR, and demonstrate that tumor selectivity can be improved by combining therapeutic EGFR mAb with an antibody against EGFRvIII. |
Databáze: | OpenAIRE |
Externí odkaz: |