An Anti-HER2 monoclonal antibody H2Mab-41 exerts antitumor activities in mouse xenograft model using dog HER2-overexpressed cells

Nami Tateyama, Teizo Asano, Tomokazu Ohishi, Junko Takei, Hideki Hosono, Ren Nanamiya, Tomohiro Tanaka, Masato Sano, Masaki Saito, Manabu Kawada, Mika K. Kaneko, Yukinari Kato

Research output: Contribution to journalArticlepeer-review

Abstract

Overexpression of human epidermal growth factor receptor 2 (HER2) has been reported in a variety of cancer types, including breast, lung, gastric, pancreatic, and colorectal cancers. Trastuzumab, a humanized anti-HER2 monoclonal antibody (mAb), has been shown to provide significant survival benefits in HER2-overexpressing breast cancer and gastric cancer patients. Previously, an anti-HER2 mAb, H2Mab-41 (IgG2b, kappa), was developed in our laboratory and its antitumor activity was demonstrated in mouse xenograft models of human colon cancer. The present study aimed to investigate the ability of H2Mab-41 to induce antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in dog HER2 (dHER2)-overexpressed cell lines, and thus exert its antitumor activity against dHER2-overexpressed tumors in vivo. Flow cytometry results demonstrated the cross-reactivity of H2Mab-41 with dHER2. Further evaluation of interaction between H2Mab-41 and dHER2-overexpressed CHO-K1 (CHO/dHER2) cells indicated moderate binding affinity of H2Mab-41 toward dHER2, with a dissociation constant (KD) of 2.6 × 10-8 M. In vitro analysis revealed that the administration of H2Mab-41 induced high levels of ADCC and CDC in CHO/dHER2 cells. Furthermore, intraperitoneal administration of H2Mab-41 in mouse xenograft models of CHO/dHER2 resulted in significant inhibition of tumor development compared to the control mouse IgG. Thus, the findings of the present study demonstrated the in vivo safety and efficacy of H2Mab-41, highlighting its suitability to be included as a part of a therapeutic regimen for dHER2-expressing canine cancers.

Original languageEnglish
Pages (from-to)184-190
Number of pages7
JournalMonoclonal antibodies in immunodiagnosis and immunotherapy
Volume40
Issue number4
DOIs
Publication statusPublished - 2021 Aug 1
Externally publishedYes

Keywords

  • ADCC
  • CDC
  • HER2
  • antitumor activity
  • monoclonal antibody

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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