Cargando…
Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells
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 activi...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849019/ https://www.ncbi.nlm.nih.gov/pubmed/27092488 http://dx.doi.org/10.3390/ijms17040563 |
_version_ | 1782429470930501632 |
---|---|
author | Li, Ruilin Hu, Siyi Chang, Yan Zhang, Zhihui Zha, Zhao Huang, Hui Shen, Guodong Liu, Jing Song, Lihua Wei, Wei |
author_facet | Li, Ruilin Hu, Siyi Chang, Yan Zhang, Zhihui Zha, Zhao Huang, Hui Shen, Guodong Liu, Jing Song, Lihua Wei, Wei |
author_sort | Li, Ruilin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4849019 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-48490192016-05-04 Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells Li, Ruilin Hu, Siyi Chang, Yan Zhang, Zhihui Zha, Zhao Huang, Hui Shen, Guodong Liu, Jing Song, Lihua Wei, Wei Int J Mol Sci Article 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. MDPI 2016-04-15 /pmc/articles/PMC4849019/ /pubmed/27092488 http://dx.doi.org/10.3390/ijms17040563 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Li, Ruilin Hu, Siyi Chang, Yan Zhang, Zhihui Zha, Zhao Huang, Hui Shen, Guodong Liu, Jing Song, Lihua Wei, Wei Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells |
title | Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells |
title_full | Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells |
title_fullStr | Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells |
title_full_unstemmed | Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells |
title_short | Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells |
title_sort | development and characterization of a humanized anti-her2 antibody hua21 with potent anti-tumor properties in breast cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849019/ https://www.ncbi.nlm.nih.gov/pubmed/27092488 http://dx.doi.org/10.3390/ijms17040563 |
work_keys_str_mv | AT liruilin developmentandcharacterizationofahumanizedantiher2antibodyhua21withpotentantitumorpropertiesinbreastcancercells AT husiyi developmentandcharacterizationofahumanizedantiher2antibodyhua21withpotentantitumorpropertiesinbreastcancercells AT changyan developmentandcharacterizationofahumanizedantiher2antibodyhua21withpotentantitumorpropertiesinbreastcancercells AT zhangzhihui developmentandcharacterizationofahumanizedantiher2antibodyhua21withpotentantitumorpropertiesinbreastcancercells AT zhazhao developmentandcharacterizationofahumanizedantiher2antibodyhua21withpotentantitumorpropertiesinbreastcancercells AT huanghui developmentandcharacterizationofahumanizedantiher2antibodyhua21withpotentantitumorpropertiesinbreastcancercells AT shenguodong developmentandcharacterizationofahumanizedantiher2antibodyhua21withpotentantitumorpropertiesinbreastcancercells AT liujing developmentandcharacterizationofahumanizedantiher2antibodyhua21withpotentantitumorpropertiesinbreastcancercells AT songlihua developmentandcharacterizationofahumanizedantiher2antibodyhua21withpotentantitumorpropertiesinbreastcancercells AT weiwei developmentandcharacterizationofahumanizedantiher2antibodyhua21withpotentantitumorpropertiesinbreastcancercells |