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Treatment of hepatocellular carcinoma with a GPC3-targeted bispecific T cell engager
There are limited strategies for the treatment of hepatocellular carcinoma (HCC). In this study, we prepared a Bispecific T cell engager (BiTE) targeting Glypican 3 (GPC3) and CD3. The GPC3/CD3 BiTE was prepared by fusing the single-chain variable fragment (scFv) of the humanized anti-GPC3 antibody...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581077/ https://www.ncbi.nlm.nih.gov/pubmed/28881778 http://dx.doi.org/10.18632/oncotarget.17905 |
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author | Bi, Yanyu Jiang, Hua Wang, Peng Song, Bo Wang, Huamao Kong, Xianming Li, Zonghai |
author_facet | Bi, Yanyu Jiang, Hua Wang, Peng Song, Bo Wang, Huamao Kong, Xianming Li, Zonghai |
author_sort | Bi, Yanyu |
collection | PubMed |
description | There are limited strategies for the treatment of hepatocellular carcinoma (HCC). In this study, we prepared a Bispecific T cell engager (BiTE) targeting Glypican 3 (GPC3) and CD3. The GPC3/CD3 BiTE was prepared by fusing the single-chain variable fragment (scFv) of the humanized anti-GPC3 antibody (9F2) with the scFv of the anti-CD3 antibody (OKT3). The in vitro and in vivo cytotoxic activities of the GPC3/CD3 BiTE were evaluated against various HCC cell lines. The GPC3/CD3 BiTE could efficiently mediate the T cell killing of GPC3-positive HCC in vitro, which was dependent on GPC3 expression on the surface of HCC cells. Moreover, our study indicates that, in the presence of the GPC3/CD3 BiTE, T cells could efficiently destroy GPC3-positive human HCC cells in vitro and in vivo. Additionally, our study further proved that GPC3 is not expressed in normal tissues. Thus, GPC3 may be a cancer-specific antigen. Collectively, these findings suggest that this anti-GPC3 BiTE might be a promising anti-tumor reagent for patients with GPC3-positive HCC. |
format | Online Article Text |
id | pubmed-5581077 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-55810772017-09-06 Treatment of hepatocellular carcinoma with a GPC3-targeted bispecific T cell engager Bi, Yanyu Jiang, Hua Wang, Peng Song, Bo Wang, Huamao Kong, Xianming Li, Zonghai Oncotarget Research Paper There are limited strategies for the treatment of hepatocellular carcinoma (HCC). In this study, we prepared a Bispecific T cell engager (BiTE) targeting Glypican 3 (GPC3) and CD3. The GPC3/CD3 BiTE was prepared by fusing the single-chain variable fragment (scFv) of the humanized anti-GPC3 antibody (9F2) with the scFv of the anti-CD3 antibody (OKT3). The in vitro and in vivo cytotoxic activities of the GPC3/CD3 BiTE were evaluated against various HCC cell lines. The GPC3/CD3 BiTE could efficiently mediate the T cell killing of GPC3-positive HCC in vitro, which was dependent on GPC3 expression on the surface of HCC cells. Moreover, our study indicates that, in the presence of the GPC3/CD3 BiTE, T cells could efficiently destroy GPC3-positive human HCC cells in vitro and in vivo. Additionally, our study further proved that GPC3 is not expressed in normal tissues. Thus, GPC3 may be a cancer-specific antigen. Collectively, these findings suggest that this anti-GPC3 BiTE might be a promising anti-tumor reagent for patients with GPC3-positive HCC. Impact Journals LLC 2017-05-16 /pmc/articles/PMC5581077/ /pubmed/28881778 http://dx.doi.org/10.18632/oncotarget.17905 Text en Copyright: © 2017 Bi et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Bi, Yanyu Jiang, Hua Wang, Peng Song, Bo Wang, Huamao Kong, Xianming Li, Zonghai Treatment of hepatocellular carcinoma with a GPC3-targeted bispecific T cell engager |
title | Treatment of hepatocellular carcinoma with a GPC3-targeted bispecific T cell engager |
title_full | Treatment of hepatocellular carcinoma with a GPC3-targeted bispecific T cell engager |
title_fullStr | Treatment of hepatocellular carcinoma with a GPC3-targeted bispecific T cell engager |
title_full_unstemmed | Treatment of hepatocellular carcinoma with a GPC3-targeted bispecific T cell engager |
title_short | Treatment of hepatocellular carcinoma with a GPC3-targeted bispecific T cell engager |
title_sort | treatment of hepatocellular carcinoma with a gpc3-targeted bispecific t cell engager |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581077/ https://www.ncbi.nlm.nih.gov/pubmed/28881778 http://dx.doi.org/10.18632/oncotarget.17905 |
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