A Novel Small Molecular Antibody, HER2-Nanobody, Inhibits Tumor Proliferation in HER2-Positive Breast Cancer Cells In Vitro and In Vivo

Breast cancer is the most common malignant cancer in women worldwide, especially in developing countries. Herceptin is a monoclonal antibody with an antitumor effect in HER2-positive breast cancer. However, the large molecular weight of Herceptin limited its employment. In this study, we constructed...

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Published inFrontiers in oncology Vol. 11; p. 669393
Main Authors Yan, Yan, Cheng, Xiao, Li, Lin, Zhang, Rumeng, Zhu, Yong, Wu, Zhengsheng, Ding, Keshuo
Format Journal Article
LanguageEnglish
Published Frontiers Media S.A 12.05.2021
Subjects
breast cancer
domain antibody
HER2
HER2-VHH
nanobody
Oncology
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Summary:Breast cancer is the most common malignant cancer in women worldwide, especially in developing countries. Herceptin is a monoclonal antibody with an antitumor effect in HER2-positive breast cancer. However, the large molecular weight of Herceptin limited its employment. In this study, we constructed and screened HER2-nanobody and verified its tumor-suppressive effect in HER2-positive breast cancer cells. HER2-nanobody was established, filtrated, purified, and was demonstrated to inhibit cell total number, viability, colony formation and mitosis, and promote cell apoptosis in HER2-positive breast cancer cells in vitro . Treated with HER2-nanobody, tumor growth was significantly inhibited by both intratumor injection and tail intravenous injection in vivo . The phosphorylation of ERK and AKT was restrained by HER2-nanobody in HER2-positive breast cancer cells. RAS-RAF-MAPK and PI3K-AKT-mTOR are two important pathways involved in HER2. It was credible for HER2-nanobody to play the tumor suppressive role by inhibiting the phosphorylation of ERK and AKT. Therefore, HER2-nanobody could be employed as a small molecular antibody to suppress HER2-positive breast cancer.
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These authors have contributed equally to this work
This article was submitted to Breast Cancer, a section of the journal Frontiers in Oncology
Edited by: Guocan Wang, University of Texas MD Anderson Cancer Center, United States
Reviewed by: Serge Muyldermans, Vrije University Brussel, Belgium; Sarah Boyle, Centre for Cancer Biology (CCB), Australia
ISSN:2234-943X
2234-943X
DOI:10.3389/fonc.2021.669393