Anti‑HER3 monoclonal antibody exerts antitumor activity in a mouse model of colorectal adenocarcinoma

Asano,Teizo; Ohishi,Tomokazu; Takei,Junko; Nakamura,Takuro; Nanamiya,Ren; Hosono,Hideki; Tanaka,Tomohiro; Sano,Masato; Harada,Hiroyuki; Kawada,Manabu; Kaneko,Mika K.; Kato,Yukinari

doi:10.3892/or.2021.8124

Anti‑HER3 monoclonal antibody exerts antitumor activity in a mouse model of colorectal adenocarcinoma

Authors:
- Teizo Asano
- Tomokazu Ohishi
- Junko Takei
- Takuro Nakamura
- Ren Nanamiya
- Hideki Hosono
- Tomohiro Tanaka
- Masato Sano
- Hiroyuki Harada
- Manabu Kawada
- Mika K. Kaneko
- Yukinari Kato
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Affiliations: Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980‑8575, Japan, Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, Numazu‑shi, Shizuoka 410‑0301, Japan, Department of Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo‑ku, Tokyo 113‑8510, Japan
Published online on: June 28, 2021 https://doi.org/10.3892/or.2021.8124
Article Number: 173
Copyright: © Asano et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

HER3 belongs to the epidermal growth factor receptor (EGFR) family and is known to form an active heterodimer with other three family members EGFR, HER2, and HER4. HER3 is overexpressed in lung, breast, colon, prostate, and gastric cancers. In the present study, we developed and validated an anti‑HER3 monoclonal antibody (mAb), H₃Mab‑17 (IgG_2a, kappa), by immunizing mice with HER3‑overexpressed CHO‑K1 cells (CHO/HER3). H₃Mab‑17 was found to react specifically with endogenous HER3 in colorectal carcinoma cell lines, using flow cytometry. The K_D for H₃Mab‑17 in CHO/HER3 and Caco‑2 (a colon cancer cell line) were determined to be 3.0x10^‑9 M and 1.5x10^‑9 M via flow cytometry, respectively, suggesting high binding affinity of H₃Mab‑17 to HER3. Then, we assessed the H₃Mab‑17 antibody‑dependent cellular cytotoxicity (ADCC) and complement‑dependent cytotoxicity (CDC) against Caco‑2, and evaluated its antitumor capacity in a Caco‑2 xenograft model. In vitro experiments revealed H₃Mab‑17 had strongly induced both ADCC and CDC against Caco‑2 cells. In vivo experiments on Caco‑2 xenografts revealed that H₃Mab‑17 treatment significantly reduced tumor growth compared with the control mouse IgG. These data indicated that H₃Mab‑17 could be a promising treatment option for HER3‑expressing colon cancers.

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