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Targeting EGFR‐positive cancer cells with cetuximab–ZZ‐PE38: Results of in vitro and in vivo studies
Author(s) -
Barnea Itay,
BenYosef Rahamim,
Karaush Victoria,
Benhar Itai,
Vexler Akiva
Publication year - 2013
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.23093
Subject(s) - cetuximab , in vivo , in vitro , flow cytometry , epidermal growth factor receptor , cancer research , cancer cell , chemistry , antibody , microbiology and biotechnology , cancer , cell culture , egfr inhibitors , monoclonal antibody , biology , medicine , immunology , biochemistry , genetics
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. © 2012 Wiley Periodicals, Inc. Head Neck, 2013