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

Yan Yan; Xiao Cheng; Lin Li; Rumeng Zhang; Yong Zhu; Zhengsheng Wu; Keshuo Ding

doi:10.3389/fonc.2021.669393

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

Front Oncol. 2021 May 12:11:669393. doi: 10.3389/fonc.2021.669393. eCollection 2021.

Authors

Yan Yan^{1

2}, Xiao Cheng¹, Lin Li¹, Rumeng Zhang¹, Yong Zhu³, Zhengsheng Wu^{1

4}, Keshuo Ding^{1

4}

Affiliations

¹ Department of Pathology, School of Basic Medicine, Anhui Medical University, Hefei, China.
² Key Laboratory of Flexible Electronics (KLOFE), Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing, China.
³ Department of Pathophysiology, School of Basic Medicine, Anhui Medical University, Hefei, China.
⁴ Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Abstract

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.

Keywords: HER2; HER2-VHH; breast cancer; domain antibody; nanobody.