Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy

Haitao Pan,1,2 Jiayu Liu,1,2 Wentong Deng,1,2 Jieyu Xing,1,2 Qing Li,1,2 Zhong Wang1,2 1School of Pharmaceutical Sciences, 2Centre for Cellular & Structural Biology, Sun Yat-Sen University, Guangzhou, People’s Republic of China Introduction: Bispecific antibodies that engage immu...

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Autores principales:	Pan H, Liu J, Deng W, Xing J, Li Q, Wang Z
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Fab nanobody PEGylation bispecific antibody half-life CEA Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/cb78cf8b29e247939918250ecc55b620
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spelling	oai:doaj.org-article:cb78cf8b29e247939918250ecc55b6202021-12-02T07:10:06ZSite-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy1178-2013https://doaj.org/article/cb78cf8b29e247939918250ecc55b6202018-05-01T00:00:00Zhttps://www.dovepress.com/site-specific-pegylation-of-an-anti-ceacd3-bispecific-antibody-improve-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Haitao Pan,1,2 Jiayu Liu,1,2 Wentong Deng,1,2 Jieyu Xing,1,2 Qing Li,1,2 Zhong Wang1,2 1School of Pharmaceutical Sciences, 2Centre for Cellular & Structural Biology, Sun Yat-Sen University, Guangzhou, People’s Republic of China Introduction: Bispecific antibodies that engage immune cells to kill cancer cells are actively pursued in cancer immunotherapy. Different types of bispecific antibodies, including single-chain fragments, Fab fragments, nanobodies, and immunoglobulin Gs (IgGs), have been studied. However, the low molecular weight of bispecific antibodies with single-chain or Fab fragments generally leads to their rapid clearance in vivo, which limits the therapeutic potential of these bispecific antibodies. Materials and methods: In this study, we used a site-specific PEGylation strategy to modify the bispecific single-domain antibody-linked Fab (S-Fab), which was designed by linking an anticarcinoembryonic antigen (anti-CEA) nanobody with an anti-CD3 Fab. Results: The half-life (t1/2) of PEGylated S-Fab (polyethylene glycol-S-Fab) was increased 12-fold in vivo with a slightly decreased tumor cell cytotoxicity in vitro as well as more potent tumor growth inhibition in vivo compared to S-Fab. Conclusion: This study demonstrated that PEGylation is an effective approach to enhance the antitumor efficacy of bispecific antibodies. Keywords: Fab, nanobody, PEGylation, bispecific antibody, half-life, CEAPan HLiu JDeng WXing JLi QWang ZDove Medical PressarticleFabnanobodyPEGylationbispecific antibodyhalf-lifeCEAMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3189-3201 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Fab nanobody PEGylation bispecific antibody half-life CEA Medicine (General) R5-920
spellingShingle	Fab nanobody PEGylation bispecific antibody half-life CEA Medicine (General) R5-920 Pan H Liu J Deng W Xing J Li Q Wang Z Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy
description	Haitao Pan,1,2 Jiayu Liu,1,2 Wentong Deng,1,2 Jieyu Xing,1,2 Qing Li,1,2 Zhong Wang1,2 1School of Pharmaceutical Sciences, 2Centre for Cellular & Structural Biology, Sun Yat-Sen University, Guangzhou, People’s Republic of China Introduction: Bispecific antibodies that engage immune cells to kill cancer cells are actively pursued in cancer immunotherapy. Different types of bispecific antibodies, including single-chain fragments, Fab fragments, nanobodies, and immunoglobulin Gs (IgGs), have been studied. However, the low molecular weight of bispecific antibodies with single-chain or Fab fragments generally leads to their rapid clearance in vivo, which limits the therapeutic potential of these bispecific antibodies. Materials and methods: In this study, we used a site-specific PEGylation strategy to modify the bispecific single-domain antibody-linked Fab (S-Fab), which was designed by linking an anticarcinoembryonic antigen (anti-CEA) nanobody with an anti-CD3 Fab. Results: The half-life (t1/2) of PEGylated S-Fab (polyethylene glycol-S-Fab) was increased 12-fold in vivo with a slightly decreased tumor cell cytotoxicity in vitro as well as more potent tumor growth inhibition in vivo compared to S-Fab. Conclusion: This study demonstrated that PEGylation is an effective approach to enhance the antitumor efficacy of bispecific antibodies. Keywords: Fab, nanobody, PEGylation, bispecific antibody, half-life, CEA
format	article
author	Pan H Liu J Deng W Xing J Li Q Wang Z
author_facet	Pan H Liu J Deng W Xing J Li Q Wang Z
author_sort	Pan H
title	Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy
title_short	Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy
title_full	Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy
title_fullStr	Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy
title_full_unstemmed	Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy
title_sort	site-specific pegylation of an anti-cea/cd3 bispecific antibody improves its antitumor efficacy
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/cb78cf8b29e247939918250ecc55b620
work_keys_str_mv	AT panh sitespecificpegylationofananticeacd3bispecificantibodyimprovesitsantitumorefficacy AT liuj sitespecificpegylationofananticeacd3bispecificantibodyimprovesitsantitumorefficacy AT dengw sitespecificpegylationofananticeacd3bispecificantibodyimprovesitsantitumorefficacy AT xingj sitespecificpegylationofananticeacd3bispecificantibodyimprovesitsantitumorefficacy AT liq sitespecificpegylationofananticeacd3bispecificantibodyimprovesitsantitumorefficacy AT wangz sitespecificpegylationofananticeacd3bispecificantibodyimprovesitsantitumorefficacy
_version_	1718399602835587072

Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy

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