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Int. J. Mol. Sci. 2016, 17(4), 563; doi:10.3390/ijms17040563

Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells

1
Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, China
2
Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei 230032, China
3
Department of Pharmacy, the Third Affiliated Hospital of Anhui Medical University, Hefei 230032, China
4
School of Life Science, University of Science and Technology of China, Hefei 230026, China
5
Anke Biotechnology Co., Ltd., Hefei 230088, China
6
Hefei Hanke Mab Biotechnology Co., Ltd., Hefei 230088, China
*
Authors to whom correspondence should be addressed.
Academic Editor: M. Rita I. Young
Received: 20 January 2016 / Revised: 31 March 2016 / Accepted: 5 April 2016 / Published: 15 April 2016
View Full-Text   |   Download PDF [3328 KB, uploaded 15 April 2016]   |  

Abstract

Human epidermal growth factor receptor 2 (HER2) is one of the most studied tumor-associated antigens for cancer immunotherapy. An engineered anti-HER-2 chimeric A21 antibody (chA21) is a chimeric antibody targeted to subdomain I of the HER2 extracellular domain. Here, we report the anti-tumor activity of the novel engineered monoclonal antibody humanized chA21 (HuA21) that targets HER2 on the basis of chA21, and we describe the underlying mechanisms. Our results reveal that HuA21 markedly inhibits the proliferation and migration of HER2-overexpressing breast cancer cells and causes enhanced antibody-dependent cell-mediated cytotoxicity potency against HER2-overexpressing tumor cells. In particular, HuA21, but not trastuzumab (Tra), markedly suppresses growth and enhances the internalization of the antibody in Tra-resistant BT-474 breast cancer cells. These characteristics are highly associated with the intrinsic ability of HuA21 to down-regulate HER2 activation and inhibit the extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) signaling pathways. Furthermore, the combination of HuA21 with Tra synergistically enhances the anti-tumor effects in vitro and in vivo and inhibits HER2 activation and the ERK1/2 and Akt signaling pathways. Altogether, our results suggest that HuA21 may represent a unique anti-HER2 antibody with potential as a therapeutic candidate alone or in combination with other anti-HER2 reagents in cancer therapy. View Full-Text
Keywords: HuA21; therapeutic antibody; HER2; breast cancer HuA21; therapeutic antibody; HER2; breast cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Li, R.; Hu, S.; Chang, Y.; Zhang, Z.; Zha, Z.; Huang, H.; Shen, G.; Liu, J.; Song, L.; Wei, W. Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells. Int. J. Mol. Sci. 2016, 17, 563.

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