A single-domain antibody-linked Fab bispecific antibody Her2-S-Fab has potent cytotoxicity against Her2-expressing tumor cells

Her2, which is frequently overexpressed in breast cancer, is one of the most studied tumor-associated antigens for cancer therapy. Anti-HER2 monoclonal antibody, trastuzumab, has achieved significant clinical benefits in metastatic breast cancer. In this study, we describe a novel bispecific antibod...

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Detalles Bibliográficos
Autores principales: Li, Aifen, Xing, Jieyu, Li, Li, Zhou, Changhua, Dong, Bin, He, Ping, Li, Qing, Wang, Zhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2016
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844577/
https://www.ncbi.nlm.nih.gov/pubmed/27112931
http://dx.doi.org/10.1186/s13568-016-0201-4
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author Li, Aifen
Xing, Jieyu
Li, Li
Zhou, Changhua
Dong, Bin
He, Ping
Li, Qing
Wang, Zhong
author_facet Li, Aifen
Xing, Jieyu
Li, Li
Zhou, Changhua
Dong, Bin
He, Ping
Li, Qing
Wang, Zhong
author_sort Li, Aifen
collection PubMed
description Her2, which is frequently overexpressed in breast cancer, is one of the most studied tumor-associated antigens for cancer therapy. Anti-HER2 monoclonal antibody, trastuzumab, has achieved significant clinical benefits in metastatic breast cancer. In this study, we describe a novel bispecific antibody Her2-S-Fab targeting Her2 by linking a single domain anti-CD16 VHH to the trastuzumab Fab. The Her2-S-Fab antibody can be efficiently expressed and purified from Escherichia coli, and drive potent cancer cell killing in HER2-overexpressing cancer cells. In xenograft model, the Her2-S-Fab suppresses tumor growth in the presence of human immune cells. Our results suggest that the bispecific Her2-S-Fab may provide a valid alternative to Her2 positive cancer therapy.
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spelling pubmed-48445772016-05-16 A single-domain antibody-linked Fab bispecific antibody Her2-S-Fab has potent cytotoxicity against Her2-expressing tumor cells Li, Aifen Xing, Jieyu Li, Li Zhou, Changhua Dong, Bin He, Ping Li, Qing Wang, Zhong AMB Express Original Article Her2, which is frequently overexpressed in breast cancer, is one of the most studied tumor-associated antigens for cancer therapy. Anti-HER2 monoclonal antibody, trastuzumab, has achieved significant clinical benefits in metastatic breast cancer. In this study, we describe a novel bispecific antibody Her2-S-Fab targeting Her2 by linking a single domain anti-CD16 VHH to the trastuzumab Fab. The Her2-S-Fab antibody can be efficiently expressed and purified from Escherichia coli, and drive potent cancer cell killing in HER2-overexpressing cancer cells. In xenograft model, the Her2-S-Fab suppresses tumor growth in the presence of human immune cells. Our results suggest that the bispecific Her2-S-Fab may provide a valid alternative to Her2 positive cancer therapy. Springer Berlin Heidelberg 2016-04-26 /pmc/articles/PMC4844577/ /pubmed/27112931 http://dx.doi.org/10.1186/s13568-016-0201-4 Text en © Li et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Li, Aifen
Xing, Jieyu
Li, Li
Zhou, Changhua
Dong, Bin
He, Ping
Li, Qing
Wang, Zhong
A single-domain antibody-linked Fab bispecific antibody Her2-S-Fab has potent cytotoxicity against Her2-expressing tumor cells
title A single-domain antibody-linked Fab bispecific antibody Her2-S-Fab has potent cytotoxicity against Her2-expressing tumor cells
title_full A single-domain antibody-linked Fab bispecific antibody Her2-S-Fab has potent cytotoxicity against Her2-expressing tumor cells
title_fullStr A single-domain antibody-linked Fab bispecific antibody Her2-S-Fab has potent cytotoxicity against Her2-expressing tumor cells
title_full_unstemmed A single-domain antibody-linked Fab bispecific antibody Her2-S-Fab has potent cytotoxicity against Her2-expressing tumor cells
title_short A single-domain antibody-linked Fab bispecific antibody Her2-S-Fab has potent cytotoxicity against Her2-expressing tumor cells
title_sort single-domain antibody-linked fab bispecific antibody her2-s-fab has potent cytotoxicity against her2-expressing tumor cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844577/
https://www.ncbi.nlm.nih.gov/pubmed/27112931
http://dx.doi.org/10.1186/s13568-016-0201-4
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