Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Antitumor Activity of an anti-EGFR/HER2 Bispecific Antibody in a Mouse Xenograft Model of Canine Osteosarcoma

Nami Tateyama
,
Hiroyuki Suzuki
* ORCID logo ,
Tomokazu Ohishi
ORCID logo ,
Teizo Asano
ORCID logo ,
Tomohiro Tanaka
,
Takuya Mizuno
,
Takeo Yoshikawa
ORCID logo ,
Manabu Kawada
,
Mika K Kaneko
,
Yukinari Kato
*
Version 1 : Received: 4 October 2022 / Approved: 5 October 2022 / Online: 5 October 2022 (09:45:16 CEST)

A peer-reviewed article of this Preprint also exists.

Tateyama, N.; Suzuki, H.; Ohishi, T.; Asano, T.; Tanaka, T.; Mizuno, T.; Yoshikawa, T.; Kawada, M.; Kaneko, M.K.; Kato, Y. Antitumor Activity of an Anti-EGFR/HER2 Bispecific Antibody in a Mouse Xenograft Model of Canine Osteosarcoma. Pharmaceutics 2022, 14, 2494. Tateyama, N.; Suzuki, H.; Ohishi, T.; Asano, T.; Tanaka, T.; Mizuno, T.; Yoshikawa, T.; Kawada, M.; Kaneko, M.K.; Kato, Y. Antitumor Activity of an Anti-EGFR/HER2 Bispecific Antibody in a Mouse Xenograft Model of Canine Osteosarcoma. Pharmaceutics 2022, 14, 2494.

Abstract

The overexpression of epidermal growth factor receptors (EGFRs) has been reported in various human tumors, including breast, gastric, lung, colorectal, and pancreatic cancers. Humanized anti‐EGFR and human epidermal growth factor receptor 2 (HER2) monoclonal antibodies (mAbs) have been shown to improve patients’ survival. Canine tumors resemble human tumors in the initiation and progression. We previously established a defucosylated mouse-dog chimeric anti‐EGFR mAb (E134Bf) and a mouse-dog chimeric anti‐HER2 mAb (H77Bf), which exerted antitumor activities in canine tumor xenograft models. Here, we produced E134Bf antibody fused to H77Bf single chain Fv at the light chains (E134Bf-H77scFv). The bispecific E134Bf-H77scFv recognized dog EGFR (dEGFR) and dog HER2 (dHER2)-overexpressed Chinese hamster ovary-K1 cells by flow cytometry. E134Bf-H77scFv also reacted with dEGFR and dHER2‐positive canine osteosarcoma D-17 cells, and possesses a high binding-affinity (KD: 1.3x10-9 M). Furthermore, E134Bf-H77scFv exerted antibody‐dependent cellular cytotoxicity and complement‐dependent cytotoxicity against D-17 cells in the presence of canine mononuclear cells and complement, respectively. Moreover, administration of E134Bf-H77scFv suppressed the development of D-17 xenograft tumor in mice early compared with the control dog IgG, E134Bf and H77Bf alone. These results indicate that E134Bf-H77scFv exerts antitumor activities against dEGFR/dHER2-positive canine tumors, and could be a valuable treatment regimen for canine tumors.

Keywords

EGFR; HER2; bispecific antibody; ADCC; CDC; canine osteosarcoma

Subject

Biology and Life Sciences, Immunology and Microbiology

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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