ORIGINAL RESEARCH article
Front. Oncol.
Sec. Breast Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1663743
This article is part of the Research TopicNovel Anti-Cancer Agents Targeting Triple-Negative Breast CancerView all 3 articles
Anti-lipolysis-stimulated lipoprotein receptor antibody-drug conjugate to treat triple-negative breast cancer
Provisionally accepted
Zhuoxin "Zora" Zhou
Davis Ballard
Tanvi VaradkarJiashuai Zhang
Zhantao DuAshley George
Aaron Krabacher
Rachel Yengo
Lufang Zhou
X. Margaret Liu*- The Ohio State University, Columbus, United States
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Abstract Triple-negative breast cancer (TNBC), the most aggressive breast cancer subtype (ER-/PR- /HER2-), is characterized by rapid proliferation, high metastatic rate and frequent recurrence. The development of targeted therapies for TNBC, such as antibody-drug conjugates (ADCs), has been limited by the lack of promising cell surface receptors. Our recent findings revealed that lipolysis-stimulated lipoprotein receptor (LSR) is overexpressed in breast cancer patients. The objective of this study was to develop an anti-LSR monoclonal antibody (mAb) and ADC for TNBC treatment. We observed high transcript and surface expression of LSR across various breast cancer subtypes, with over 63% of TNBC patient tissue samples exhibiting elevated expression. A new mAb targeting the extracellular domain of LSR was developed, engineered, and evaluated in vitro and in vivo. The ADC, constructed by conjugating LSR mAb with a cytotoxic agent mertansine (DM1), demonstrated potent anti-TNBC cytotoxicity in three cell lines. In vivo anti-cancer efficacy was evaluated in two TNBC xenografted mouse models, where a 24 mg/kg-body weight dose of LSR mAb-DM1 reduced tumor burden by 85% in one model and prevented tumor regrowth in the second model. Notably, no off-target effects or systemic toxicity were observed in animal models during or after treatment. This study highlights LSR as a promising therapeutic target and the anti-LSR mAb and ADC as potential targeted therapies for TNBC.
Keywords: lipolysis-stimulated lipoprotein receptor (LSR), antibody-drug conjugate (ADC), Triple-negative breast cancer (TNBC), targeted therapy, evaluations
Received: 10 Jul 2025; Accepted: 03 Sep 2025.
Copyright: © 2025 Zhou, Ballard, Varadkar, Zhang, Du, George, Krabacher, Yengo, Zhou and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: X. Margaret Liu, The Ohio State University, Columbus, United States
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