title: The relevance of ADCC for EGFR targeting: A review of the literature and a clinically-applicable method of assessment in patients.
abstract: BACKGROUND
  Advances in the understanding of tumor biology have led to the development of targeted therapies as monoclonal antibodies (MoAbs) in clinical oncology. Among their suggested mechanisms of action monoclonal antibodies (IgG1) selectively directed against tumor membrane receptors mediate of antibody-dependent cellular cytotoxicity (ADCC) by triggering Fc-γRIII on natural killer (NK) cells.
  
  
  METHODS
  This study reviews the clinical context of ADCC measurement with a particular focus on EGFR targeting and describes an ex vivo ADCC method applied to MoAbs (cetuximab and panitumumab), against epidermal growth factor receptor (EGFR). The test performance was evaluated on different target cells lines (CAL166, A431, HNO91, CAL27), with different effector cells (peripheral blood mononuclear cells or natural killers -NK-) and in various experimental conditions, in order to establish a truly clinically applicable method.
  
  
  RESULTS
  Using the experience available in the published literature, we optimized all variables involved in the experimental design: target cells type, numbers and ratio target cells and NK cells (effector cells) per well, time of exposure and repeatability.
  
  
  CONCLUSIONS
  ADCC measurement may be of clinical relevance in the context of treatment with MoAbs. This study describes a non-radioactive method which has proven satisfactory in terms of sensitivity, reproducibility, feasibility and cost effectiveness for the measurement of ADCC activity mediated by NK with an orientation towards the EGFR target.
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce General Hospital, Via Carle 25, 12100, Cuneo, Italy.
authors.forename: Martino
authors.initials: M
authors.lastname: Monteverde
authors.affiliation: Oncopharmacology unit, Centre Antoine Lacassagne, Nice, France.
authors.forename: Gerard
authors.initials: G
authors.lastname: Milano
authors.affiliation: Laboratory Department, S. Croce General Hospital, Cuneo, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Strola
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce General Hospital, Via Carle 25, 12100, Cuneo, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Maffi
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce General Hospital, Via Carle 25, 12100, Cuneo, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Lattanzio
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce General Hospital, Via Carle 25, 12100, Cuneo, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vivenza
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce General Hospital, Via Carle 25, 12100, Cuneo, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Tonissi
authors.affiliation: Medical Oncology, Oncology Department, S. Croce General Hospital, Cuneo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Merlano
authors.affiliation: Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce General Hospital, Via Carle 25, 12100, Cuneo, Italy. Electronic address: lonigro.c@ospedale.cuneo.it.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Lo Nigro
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D000068818:Cetuximab / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077544:Panitumumab
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: ADCC; Antitumor monoclonal antibody; Cellular immunity; Cetuximab; Natural Killer