Open Access

Defucosylated mouse‑dog chimeric anti‑HER2 monoclonal antibody exerts antitumor activities in mouse xenograft models of canine tumors

  • Authors:
    • Hiroyuki Suzuki
    • Tomokazu Ohishi
    • Teizo Asano
    • Tomohiro Tanaka
    • Masaki Saito
    • Takuya Mizuno
    • Takeo Yoshikawa
    • Manabu Kawada
    • Mika K. Kaneko
    • Yukinari Kato
  • View Affiliations

  • Published online on: July 15, 2022     https://doi.org/10.3892/or.2022.8366
  • Article Number: 154
  • Copyright: © Suzuki et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Human epidermal growth factor receptor 2 (HER2) overexpression has been reported in various types of cancer, including breast, gastric, lung, colorectal and pancreatic cancer. A humanized anti‑HER2 monoclonal antibody (mAb), trastuzumab, has been shown to improve survival of patients in HER2‑positive breast and gastric cancer. An anti‑HER2 mAb, H2Mab‑77 (mouse IgG1, kappa) was previously developed. In the present study, a defucosylated version of mouse‑dog chimeric anti‑HER2 mAb (H77Bf) was generated. H77Bf possesses a high binding‑affinity [a dissociation constant (KD): 7.5x10‑10 M, as determined by flow cytometric analysis] for dog HER2‑overexpressed CHO‑K1 (CHO/dHER2) cells. H77Bf highly exerted antibody‑dependent cellular cytotoxicity (ADCC) and complement‑dependent cytotoxicity (CDC) for CHO/dHER2 cells by canine mononuclear cells and complement, respectively. Moreover, administration of H77Bf significantly suppressed the development of CHO/dHER2 xenograft tumor in mice compared with the control dog IgG. H77Bf also possesses a high binding‑affinity (KD: 7.2x10‑10 M) for a canine mammary gland tumor cell line (SNP), and showed high ADCC and CDC activities for SNP cells. Intraperitoneal administration of H77Bf in mouse xenograft models of SNP significantly suppressed the development of SNP xenograft tumors compared with the control dog IgG. These results indicated that H77Bf exerts antitumor activities against dHER2‑positive canine cancers, and could be valuable treatment regimen for canine cancers.

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September-2022
Volume 48 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Suzuki H, Ohishi T, Asano T, Tanaka T, Saito M, Mizuno T, Yoshikawa T, Kawada M, Kaneko MK, Kato Y, Kato Y, et al: Defucosylated mouse‑dog chimeric anti‑HER2 monoclonal antibody exerts antitumor activities in mouse xenograft models of canine tumors. Oncol Rep 48: 154, 2022
APA
Suzuki, H., Ohishi, T., Asano, T., Tanaka, T., Saito, M., Mizuno, T. ... Kato, Y. (2022). Defucosylated mouse‑dog chimeric anti‑HER2 monoclonal antibody exerts antitumor activities in mouse xenograft models of canine tumors. Oncology Reports, 48, 154. https://doi.org/10.3892/or.2022.8366
MLA
Suzuki, H., Ohishi, T., Asano, T., Tanaka, T., Saito, M., Mizuno, T., Yoshikawa, T., Kawada, M., Kaneko, M. K., Kato, Y."Defucosylated mouse‑dog chimeric anti‑HER2 monoclonal antibody exerts antitumor activities in mouse xenograft models of canine tumors". Oncology Reports 48.3 (2022): 154.
Chicago
Suzuki, H., Ohishi, T., Asano, T., Tanaka, T., Saito, M., Mizuno, T., Yoshikawa, T., Kawada, M., Kaneko, M. K., Kato, Y."Defucosylated mouse‑dog chimeric anti‑HER2 monoclonal antibody exerts antitumor activities in mouse xenograft models of canine tumors". Oncology Reports 48, no. 3 (2022): 154. https://doi.org/10.3892/or.2022.8366