Cetuximab-mediated antibody-dependent cellular cytotoxicity activity against colorectal cancer cell lines

Kosuke Yamaguchi, Kuniyuki Katano, Kiyoshi Hashimoto, Hiroki Chikumi, Jun Kurai, Takashi Sumikawa, Naoki Kinoshita, Kazuhiko Yoneda, Masaki Nakamoto, Toshiyuki Tatsukawa, Yasushi Shigeoka, Hisashi Suyama, Tadashi Igishi, Naoto Burioka, Masahide Ikeguchi, Eiji Shimizu

Research output: Contribution to journalArticlepeer-review

Abstract

Cetuximab is a chimeric mouse-human antibody targeting the extracellular domain of epidermal growth factor receptor (EGFR), and is much-anticipated to improve colorectal cancer therapy. In addition to inhibitory properties, cetuximab has immunologic anti-tumor effects, and antibody-dependent cellular cytotoxicity (ADCC) activity, which has not been well studied. In this study, we investigated the ADCC activity of cetuximab against colorectal cancer (CRC) cell lines. We examined the correlation between EGFR expression in six CRC cell lines and ADCC activity of cetuximab. EGFR expression was measured by a quantitative flow cytometric analysis. The ADCC was assessed by a 4-h 51Cr release assay. In addition, we assessed the influence of interleukin-2 (IL-2) and chemotherapy on ADCC activity. Cetuximab showed no growth inhibitory effect in any of the cell lines, whereas it showed maximum ADCC activity at a very low concentration of 0.025 μg/ml. A logistic correlation was observed between the number of EGFRs and ADCC activity. ADCC was enhanced at any EGFR expression level in the presence of IL-2. The postoperative adjuvant chemotherapy in CRC patients using oral fluorinated pyrimidine did not inhibit ADCC activity. These results suggest that the ADCC plays an important role in the anti-tumor mechanism of cetuximab against CRC.

Original languageEnglish (US)
Pages (from-to)423-430
Number of pages8
JournalBiotherapy
Volume22
Issue number6
StatePublished - Nov 1 2008

Keywords

  • Antibody-dependent cellular cytotoxicity (ADCC)
  • Cetuximab
  • Colorectal cancer (CRC)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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