Augmentation of antibody-dependent cellular cytotoxicity with defucosylated monoclonal antibodies in patients with GI-tract cancer

  • Authors:
    • Takahiro Nakajima
    • Hirokazu Okayama
    • Mai Ashizawa
    • Masaru Noda
    • Keita Aoto
    • Motonobu Saito
    • Tomoyuki Monma
    • Shinji Ohki
    • Masahiko Shibata
    • Seiichi Takenoshita
    • Koji Kono
  • View Affiliations

  • Published online on: December 8, 2017     https://doi.org/10.3892/ol.2017.7556
  • Pages:2604-2610
Metrics: HTML 0 views | PDF 0 views     Cited By: 0 citations

Abstract

Enhancement of antibody-dependent cellular cytotoxicity (ADCC) with some modalities may be a promising approach to enhance the efficacy of therapeutic monoclonal antibodies (mAbs). It has previously been demonstrated that the removal of fucose from antibody oligosaccharides (defucosylation) leads to augmentation of ADCC activity. To establish clinically relevant evidence of this procedure, the present study evaluated trastuzumab‑ and cetuximab‑mediated ADCC by comparing defucosylated mAbs with conventional mAbs using peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from 20 patients with gastrointestinal tract cancer and 10 healthy volunteers. ADCCs were measured using PBMCs as effector cells and two gastric cancer cell lines as target cells. ADCCs were significantly enhanced with defucosylated mAbs compared with conventional mAbs using PBMC from the healthy donors and patients with cancer. The results confirmed that the cetuximab‑ and trastuzumab‑mediated ADCCs in advanced disease were impaired in comparison to those in early disease or healthy individuals. However, when the defucosylated mAbs were used instead of the conventional mAbs, the ADCC activities in the advanced cases were almost comparable with those in early disease or healthy individuals. Furthermore, the expression of ADCC associated molecules were modified toward immunosuppressive status with a mitogen‑activated protein kinase inhibitor in vitro, the conventional cetuximab‑ and trastuzumab‑mediated ADCC was downregulated, and the defucosylated mAbs overcome the downregulation of ADCC. In conclusion, defucosylated therapeutic mAbs may enhance ADCC activities in patients with cancer, which may lead to more effective anti‑cancer treatments.

Related Articles

Journal Cover

February 2018
Volume 15 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Nakajima, T., Okayama, H., Ashizawa, M., Noda, M., Aoto, K., Saito, M. ... Kono, K. (2018). Augmentation of antibody-dependent cellular cytotoxicity with defucosylated monoclonal antibodies in patients with GI-tract cancer. Oncology Letters, 15, 2604-2610. https://doi.org/10.3892/ol.2017.7556
MLA
Nakajima, T., Okayama, H., Ashizawa, M., Noda, M., Aoto, K., Saito, M., Monma, T., Ohki, S., Shibata, M., Takenoshita, S., Kono, K."Augmentation of antibody-dependent cellular cytotoxicity with defucosylated monoclonal antibodies in patients with GI-tract cancer". Oncology Letters 15.2 (2018): 2604-2610.
Chicago
Nakajima, T., Okayama, H., Ashizawa, M., Noda, M., Aoto, K., Saito, M., Monma, T., Ohki, S., Shibata, M., Takenoshita, S., Kono, K."Augmentation of antibody-dependent cellular cytotoxicity with defucosylated monoclonal antibodies in patients with GI-tract cancer". Oncology Letters 15, no. 2 (2018): 2604-2610. https://doi.org/10.3892/ol.2017.7556