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Breast Cancer Research
Published in: Breast Cancer Research 1/2021

Open Access 01-12-2021 | Metastasis | Research article

Leronlimab, a humanized monoclonal antibody to CCR5, blocks breast cancer cellular metastasis and enhances cell death induced by DNA damaging chemotherapy

Authors: Xuanmao Jiao, Min Wang, Zhao Zhang, Zhiping Li, Dong Ni, Anthony W. Ashton, Hsin-Yao Tang, David W. Speicher, Richard G. Pestell

Published in: Breast Cancer Research | Issue 1/2021

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Abstract

Background

Triple-negative breast cancer (BCa) (TNBC) is a deadly form of human BCa with limited treatment options and poor prognosis. In our prior analysis of over 2200 breast cancer samples, the G protein-coupled receptor CCR5 was expressed in > 95% of TNBC samples. A humanized monoclonal antibody to CCR5 (leronlimab), used in the treatment of HIV-infected patients, has shown minimal side effects in large patient populations.

Methods

A humanized monoclonal antibody to CCR5, leronlimab, was used for the first time in tissue culture and in mice to determine binding characteristics to human breast cancer cells, intracellular signaling, and impact on (i) metastasis prevention and (ii) impact on established metastasis.

Results

Herein, leronlimab was shown to bind CCR5 in multiple breast cancer cell lines. Binding of leronlimab to CCR5 reduced ligand-induced Ca+ 2 signaling, invasion of TNBC into Matrigel, and transwell migration. Leronlimab enhanced the BCa cell killing of the BCa chemotherapy reagent, doxorubicin. In xenografts conducted with Nu/Nu mice, leronlimab reduced lung metastasis of the TNBC cell line, MB-MDA-231, by > 98% at 6 weeks. Treatment with leronlimab reduced the metastatic tumor burden of established TNBC lung metastasis.

Conclusions

The safety profile of leronlimab, together with strong preclinical evidence to both prevent and reduce established breast cancer metastasis herein, suggests studies of clinical efficacy may be warranted.
Appendix
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Metadata
Title
Leronlimab, a humanized monoclonal antibody to CCR5, blocks breast cancer cellular metastasis and enhances cell death induced by DNA damaging chemotherapy
Authors
Xuanmao Jiao
Min Wang
Zhao Zhang
Zhiping Li
Dong Ni
Anthony W. Ashton
Hsin-Yao Tang
David W. Speicher
Richard G. Pestell
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2021
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-021-01391-1

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