title: Targeting EGFR-positive cancer cells with cetuximab-ZZ-PE38: Results of in vitro and in vivo studies.
abstract: BACKGROUND
  Arming antibody with toxins is a new approach in cancer therapy. We evaluated the efficacy of cetuximab-ZZ-PE38 immunocomplex in killing cancer cells in vitro and inhibiting tumor growth in nude mice.
  
  
  METHODS
  Several cancer cell lines and human foreskin fibroblasts were tested for epidermal growth factor receptor (EGFR) expression and cetuximab binding using Western blot assay, enzyme-linked immunosorbent assay (ELISA), and flow cytometry. Cell survival in vitro was estimated by XTT assay. Tumor size was measured twice a week.
  
  
  RESULTS
  Cetuximab-ZZ-PE38 immunocomplex was significantly more effective in killing head and neck cancer cells than nonspecific IgG-ZZ-PE38 complex or free ZZ-PE38, whereas normal cells were not affected. Tumor treatment with immunocomplex resulted in tumor shrinkage. The immunocomplex was safe to mice at a therapeutic dosage of 0.25 mg/mL, whereas the dosage of 0.50 mg/mL induced liver toxicity.
  
  
  CONCLUSIONS
  Cetuximab-ZZ-PE38 immunocomplex is a highly effective agent in killing EGFR-positive cancer cells and in tumor shrinkage.
authors.affiliation: Radiobiology and Cancer Research Lab, Division of Oncology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Itay
authors.initials: I
authors.lastname: Barnea
authors.forename: Rahamim
authors.initials: R
authors.lastname: Ben-Yosef
authors.forename: Victoria
authors.initials: V
authors.lastname: Karaush
authors.forename: Itai
authors.initials: I
authors.lastname: Benhar
authors.forename: Akiva
authors.initials: A
authors.lastname: Vexler
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D000068818:Cetuximab; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000378:metabolism; D005098:Exotoxins / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D005098:Exotoxins; C042252:Pseudomonas exotoxin-epidermal growth factor conjugate; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D000068818:Cetuximab