An anti‑TROP2 monoclonal antibody TrMab‑6 exerts antitumor activity in breast cancer mouse xenograft models

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

doi:10.3892/or.2021.8083

An anti‑TROP2 monoclonal antibody TrMab‑6 exerts antitumor activity in breast cancer mouse xenograft models

Authors:
- Tomohiro Tanaka
- Tomokazu Ohishi
- Teizo Asano
- Junko Takei
- Ren Nanamiya
- Hideki Hosono
- 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, Aoba‑ku, 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: May 19, 2021 https://doi.org/10.3892/or.2021.8083
Article Number: 132
Copyright : © Tanaka et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Trophoblast cell surface antigen 2 (TROP2), reported to be overexpressed in several types of cancer, is involved in cell proliferation, invasion, metastasis, and poor prognosis of many types of cancer. Previously, a highly sensitive anti‑TROP2 monoclonal antibody (clone TrMab‑6; mouse IgG_2b, κ) was developed using a Cell‑Based Immunization and Screening (CBIS) method. TrMab‑6 was useful for investigations using flow cytometry, western blot, and immunohistochemistry. The aim of the present study was to investigate whether TrMab‑6 possesses in vitro antibody‑dependent cellular cytotoxicity (ADCC) or complement‑dependent cytotoxicity (CDC) activities or in vivo antitumor activities using mouse xenograft models of TROP2‑overexpressed CHO‑K1 (CHO/TROP2) and breast cancer cell lines, including MCF7, MDA‑MB‑231, and MDA‑MB‑468. In vitro experiments revealed that TrMab‑6 strongly induced ADCC and CDC activities against CHO/TROP2 and the three breast cancer cell lines, whereas it did not show those activities against parental CHO‑K1 and MCF7/TROP2‑knockout cells. Furthermore, in vivo experiments on CHO/TROP2 and MCF7 xenografts revealed that TrMab‑6 significantly reduced tumor growth, whereas it did not show antitumor activities against parental CHO‑K1 and MCF7/TROP2‑knockout xenografts. The findings suggest that TrMab‑6 is a promising treatment option for TROP2‑expressing breast cancers.

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