Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Defucosylated Monoclonal Antibody (H2Mab-139-mG2a-f) Exerted Antitumor Activities in Mouse Xenograft Models of Breast Cancers against Human Epidermal Growth Factor Receptor 2

Hiroyuki Suzuki
* ORCID logo ,
Tomokazu Ohishi
ORCID logo ,
Ren Nanamiya
ORCID logo ,
Manabu Kawada
,
Mika K Kaneko
,
Yukinari Kato
* ORCID logo
Version 1 : Received: 4 July 2023 / Approved: 4 July 2023 / Online: 4 July 2023 (09:38:15 CEST)

A peer-reviewed article of this Preprint also exists.

Suzuki, H.; Ohishi, T.; Nanamiya, R.; Kawada, M.; Kaneko, M.K.; Kato, Y. Defucosylated Monoclonal Antibody (H2Mab-139-mG2a-f) Exerted Antitumor Activities in Mouse Xenograft Models of Breast Cancers against Human Epidermal Growth Factor Receptor 2. Curr. Issues Mol. Biol. 2023, 45, 7734-7748. https://doi.org/10.3390/cimb45100488 Suzuki, H.; Ohishi, T.; Nanamiya, R.; Kawada, M.; Kaneko, M.K.; Kato, Y. Defucosylated Monoclonal Antibody (H2Mab-139-mG2a-f) Exerted Antitumor Activities in Mouse Xenograft Models of Breast Cancers against Human Epidermal Growth Factor Receptor 2. Curr. Issues Mol. Biol. 2023, 45, 7734-7748. https://doi.org/10.3390/cimb45100488

Abstract

Two monoclonal antibodies (mAbs) against human epidermal growth factor receptor 2 (HER2), trastuzumab and pertuzumab, were clinically approved. We previously developed a highly sensitive and specific anti-HER2 mAb, H2Mab-139 (mouse IgG1, kappa). In this study, we produced a defucosylated IgG2a version of anti‑HER2 mAb (H2Mab-139-mG2a-f) to enhance ADCC-mediated antitumor activity. H2Mab-139-mG2a-f exhibits a high binding affinity in flow cytometry with the dissociation constant (KD) determined to be 3.9 × 10‑9 M and 7.7 × 10‑9 M against HER2‑overexpressed Chinese hamster ovary (CHO)-K1 (CHO/HER2) and HER2-positive BT-474 cells, respectively. Moreover, we showed that H2Mab-139-mG2a-f exerted ADCC and complement-dependent cytotoxicity against CHO/HER2 and BT-474 cells in vitro and exhibited potent antitumor activities in the xenograft models. These results indicated that H2Mab-139-mG2a-f exerts antitumor effects against HER2-positive human breast cancers and could be useful for an antibody treatment regimen for HER2-positive human cancers.

Keywords

HER2; breast cancer; monoclonal antibody; antitumor activities; mouse xenograft model; antibody-dependent cellular cytotoxicity

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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