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

Suzuki,Hiroyuki; Ohishi,Tomokazu; Asano,Teizo; Tanaka,Tomohiro; Saito,Masaki; Mizuno,Takuya; Yoshikawa,Takeo; Kawada,Manabu; Kaneko,Mika K.; Kato,Yukinari

doi:10.3892/or.2022.8366

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
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Affiliations: Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980‑8575, Japan, Institute of Microbial Chemistry (BIKAKEN), Microbial Chemistry Research Foundation, Numazu, Shizuoka 410‑0301, Japan, Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980‑8575, Japan, Laboratory of Molecular Diagnostics and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi 753‑8515, Japan, Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980‑8575, Japan
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 (K_D): 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 (K_D: 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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