title: Cetuximab induce antibody-dependent cellular cytotoxicity against EGFR-expressing esophageal squamous cell carcinoma.
abstract: To evaluate the possibility of treatment with antiepidermal growth factor receptor (EGFR) mAb, Cetuximab against esophageal squamous cell carcinoma (SCC), we performed detail analysis of the antibody-dependent cellular cytotoxicity (ADCC) mediated by Cetuximab against esophageal SCC. Esophageal SCC cell lines with various levels of EGFR (n = 8) were evaluated for their Cetuximab-mediated ADCC by (51)Cr-release assay. As a result, Cetuximab was able to induce ADCC against EGFR-expressing esophageal SCC and the activities reflected the degree of EGFR expression on the esophageal SCC. The activities of Cetuximab-mediated ADCC by patients' PBMC were impaired in comparison with those by healthy donors' PBMC. Moreover, the inhibition of transforming growth factor (TGF)-beta could enhance Cetuximab-mediated ADCC against TGF-beta-producing SCC. In conclusion, Cetuximab was able to induce ADCC against EGFR-expressing esophageal SCC. Some modalities aiming at enhancing the Cetuximab-mediated ADCC may be necessary for successful Cetuximab treatment of patients with esophageal SCC.
authors.affiliation: First Department of Surgery, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Koji
authors.initials: K
authors.lastname: Kono
authors.forename: Kousaku
authors.initials: K
authors.lastname: Mimura
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Sugai
authors.forename: Hidenori
authors.initials: H
authors.lastname: Akaike
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects* / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D000068818:Cetuximab; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000276:immunology*; D004938:Esophageal Neoplasms / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000276:immunology / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007376:Interleukin-2; C509041:TGFB2 protein, human; D016211:Transforming Growth Factor alpha; D053781:Transforming Growth Factor beta2; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D000068818:Cetuximab