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CC BY 4.0 · Pharmaceutical Fronts 2023; 05(03): e187-e196
DOI: 10.1055/s-0043-1772703
Original Article

A Potential Antibody–Drug Conjugate Targeting Human LIV1 for the Treatment of Triple-Negative Breast Cancer

Wei Zhang
1   Department of Biology, China State Institute of Pharmaceutical Industry Co., Ltd., People's Republic of China
,
Hong Liu
1   Department of Biology, China State Institute of Pharmaceutical Industry Co., Ltd., People's Republic of China
,
Wei-Liang Zhuang
1   Department of Biology, China State Institute of Pharmaceutical Industry Co., Ltd., People's Republic of China
,
Yuan Li
1   Department of Biology, China State Institute of Pharmaceutical Industry Co., Ltd., People's Republic of China
,
Li-Ping Xie
1   Department of Biology, China State Institute of Pharmaceutical Industry Co., Ltd., People's Republic of China
,
You-Jia Hu
1   Department of Biology, China State Institute of Pharmaceutical Industry Co., Ltd., People's Republic of China
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Abstract

Triple-negative breast cancer (TNBC), which accounts for 15 to 20% of incidents of breast cancer, is the only breast cancer subtype that lacks targeted treatments. It was reported in the literature that LIV1 was highly expressed in TNBC and other solid tumors. This makes LIV1 a potential target for the treatment of TNBC. This study aimed to develop an anti-LIV1 antibody for the treatment of TNBC. In this study, a novel anti-LIV1 antibody Ab1120 was developed and conjugated with monomethyl auristatin E (MMAE) to obtain the antibody–drug conjugate, Ab1120-vcMMAE. The Cell Counting Kit-8 method was used to assess the killing effect of the antibody–drug conjugate on cell lines MDA-MB−231 (high LIV1 expression of breast cancer cell line), MDA-MB-468 (low LIV1 expression of breast cell line), and 293C18 (LIV1-negative human embryonic kidney cell). The antitumor effect of Ab1120-vcMMAE on an MDA-MB-231 xenograft model was determined by evaluating the tumor volume and body weight after its treatment. In vitro analysis showed that Ab1120-vcMMAE is a potent inhibitor against the proliferation of a LIV1 overexpression cell line. The in vivo results demonstrated its antitumor activity in the cell-derived xenograft breast tumor mouse model. The results of this study suggest that Ab1120-vcMMAE may be used as a new therapeutic drug for patients with LIV1 high-expression breast cancer.

Keywords

triple-negative breast cancer - LIV1 - anti-LIV1 antibody - antibody–drug conjugates

Ethical Approval

All animal experiments were approved by the Animal Ethical Committee at the China State Institute of Pharmaceutical Industry, which conformed to the National Institutes of Health Guidelines on Laboratory Research and Guide for the Care and Use of Laboratory Animals (Eighth Edition, 2011). This article does not contain any studies with human participants performed by any of the authors.




Publication History

Received: 30 March 2023

Accepted: 24 July 2023

Article published online:
24 August 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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