Open Access

Therapeutic antitumor efficacy of anti-epidermal growth factor receptor antibody, cetuximab, against malignant pleural mesothelioma

  • Authors:
    • Jun Kurai
    • Hiroki Chikumi
    • Kiyoshi Hashimoto
    • Miyako Takata
    • Takanori Sako
    • Kosuke Yamaguchi
    • Naoki Kinoshita
    • Masanari Watanabe
    • Hirokazu Touge
    • Haruhiko Makino
    • Tadashi Igishi
    • Hironobu Hamada
    • Seiji Yano
    • Eiji Shimizu
  • View Affiliations

  • Published online on: August 24, 2012     https://doi.org/10.3892/ijo.2012.1607
  • Pages: 1610-1618
  • Copyright: © Kurai et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Epidermal growth factor receptor (EGFR) is commonly overexpressed in malignant pleural mesothelioma (MPM). Cetuximab is a chimeric mouse-human antibody targeted against EGFR and induces potent antibody-dependent cellular cytotoxicity (ADCC). The action of cetuximab against MPM cells has not been well studied. Therefore, in this study, we investigated the antitumor activity of cetuximab against MPM cell lines, particularly with respect to ADCC activity in vitro and in vivo. EGFR expression of MPM cells was measured by a quantitative flow cytometric analysis and immunohistochemistry. The effect of cetuximab on growth inhibition was assessed using a modified MTT assay. The ADCC activity was measured by a 4-h 51Cr release assay using fresh or IL-2-activated peripheral blood mononuclear cells. In vivo antitumor activity of cetuximab was evaluated using an orthotopic implantation mouse model. Cetuximab-mediated ADCC activity against MPM cells was observed at low concentration (0.25 mg/ml) and was enhanced by IL-2, whereas no direct effect on growth inhibition was detected. A logarithmic correlation was observed between the number of EGFRs on MPM cells and ADCC activity. Low EGFR expression on the MPM cells, which was weakly detectable by immunohistochemistry, was sufficient for maximum ADCC activity. In the mouse model, cetuximab treatment with or without IL-2 significantly inhibited intrathoracic tumor growth and prolonged their survival. Our study shows that cetuximab has potent anti-MPM activity both in vitro and in vivo, mainly through the immunologic mechanism of ADCC. Cetuximab has the potential to be used as a novel therapy for MPM patients.
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November 2012
Volume 41 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kurai J, Chikumi H, Hashimoto K, Takata M, Sako T, Yamaguchi K, Kinoshita N, Watanabe M, Touge H, Makino H, Makino H, et al: Therapeutic antitumor efficacy of anti-epidermal growth factor receptor antibody, cetuximab, against malignant pleural mesothelioma. Int J Oncol 41: 1610-1618, 2012
APA
Kurai, J., Chikumi, H., Hashimoto, K., Takata, M., Sako, T., Yamaguchi, K. ... Shimizu, E. (2012). Therapeutic antitumor efficacy of anti-epidermal growth factor receptor antibody, cetuximab, against malignant pleural mesothelioma. International Journal of Oncology, 41, 1610-1618. https://doi.org/10.3892/ijo.2012.1607
MLA
Kurai, J., Chikumi, H., Hashimoto, K., Takata, M., Sako, T., Yamaguchi, K., Kinoshita, N., Watanabe, M., Touge, H., Makino, H., Igishi, T., Hamada, H., Yano, S., Shimizu, E."Therapeutic antitumor efficacy of anti-epidermal growth factor receptor antibody, cetuximab, against malignant pleural mesothelioma". International Journal of Oncology 41.5 (2012): 1610-1618.
Chicago
Kurai, J., Chikumi, H., Hashimoto, K., Takata, M., Sako, T., Yamaguchi, K., Kinoshita, N., Watanabe, M., Touge, H., Makino, H., Igishi, T., Hamada, H., Yano, S., Shimizu, E."Therapeutic antitumor efficacy of anti-epidermal growth factor receptor antibody, cetuximab, against malignant pleural mesothelioma". International Journal of Oncology 41, no. 5 (2012): 1610-1618. https://doi.org/10.3892/ijo.2012.1607