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BiHC, a T-Cell–Engaging Bispecific Recombinant Antibody, Has Potent Cytotoxic Activity Against Her2 Tumor Cells()

Among different cancer immunotherapy approaches, bispecific antibodies (BsAbs) are of great interest due to their ability to recruit immune cells to kill tumor cells directly. Various BsAbs against Her2 tumor cells have been proposed with potent cytotoxic activities. However, most of these formats r...

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Autores principales: Xing, Jieyu, Lin, Limin, Li, Jing, Liu, Jiayu, Zhou, Changhua, Pan, Haitao, Shu, Rui, Dong, Bin, Cao, Donglin, Li, Qing, Wang, Zhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548338/
https://www.ncbi.nlm.nih.gov/pubmed/28797938
http://dx.doi.org/10.1016/j.tranon.2017.07.003
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author Xing, Jieyu
Lin, Limin
Li, Jing
Liu, Jiayu
Zhou, Changhua
Pan, Haitao
Shu, Rui
Dong, Bin
Cao, Donglin
Li, Qing
Wang, Zhong
author_facet Xing, Jieyu
Lin, Limin
Li, Jing
Liu, Jiayu
Zhou, Changhua
Pan, Haitao
Shu, Rui
Dong, Bin
Cao, Donglin
Li, Qing
Wang, Zhong
author_sort Xing, Jieyu
collection PubMed
description Among different cancer immunotherapy approaches, bispecific antibodies (BsAbs) are of great interest due to their ability to recruit immune cells to kill tumor cells directly. Various BsAbs against Her2 tumor cells have been proposed with potent cytotoxic activities. However, most of these formats require extensive processing to obtain heterodimeric bispecific antibodies. In this study, we describe a bispecific antibody, BiHC (bispecific Her2-CD3 antibody), constructed with a single-domain anti-Her2 and a single-chain Fv (variable fragment) of anti-CD3 in an IgG-like format. In contrast to most IgG-like BsAbs, the two arms in BiHC have different molecular weights, making it easier to separate hetero- or homodimers. BiHC can be expressed in Escherichia coli and purified via Protein A affinity chromatography. The purified BiHC can recruit T cells and induce specific cytotoxicity of Her2-expressing tumor cells in vitro. The BiHC can also efficiently inhibit the tumor growth in vivo. Thus, BiHC is a promising candidate for the treatment of Her2-positive cancers.
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spelling pubmed-55483382017-08-14 BiHC, a T-Cell–Engaging Bispecific Recombinant Antibody, Has Potent Cytotoxic Activity Against Her2 Tumor Cells() Xing, Jieyu Lin, Limin Li, Jing Liu, Jiayu Zhou, Changhua Pan, Haitao Shu, Rui Dong, Bin Cao, Donglin Li, Qing Wang, Zhong Transl Oncol Original article Among different cancer immunotherapy approaches, bispecific antibodies (BsAbs) are of great interest due to their ability to recruit immune cells to kill tumor cells directly. Various BsAbs against Her2 tumor cells have been proposed with potent cytotoxic activities. However, most of these formats require extensive processing to obtain heterodimeric bispecific antibodies. In this study, we describe a bispecific antibody, BiHC (bispecific Her2-CD3 antibody), constructed with a single-domain anti-Her2 and a single-chain Fv (variable fragment) of anti-CD3 in an IgG-like format. In contrast to most IgG-like BsAbs, the two arms in BiHC have different molecular weights, making it easier to separate hetero- or homodimers. BiHC can be expressed in Escherichia coli and purified via Protein A affinity chromatography. The purified BiHC can recruit T cells and induce specific cytotoxicity of Her2-expressing tumor cells in vitro. The BiHC can also efficiently inhibit the tumor growth in vivo. Thus, BiHC is a promising candidate for the treatment of Her2-positive cancers. Neoplasia Press 2017-08-07 /pmc/articles/PMC5548338/ /pubmed/28797938 http://dx.doi.org/10.1016/j.tranon.2017.07.003 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Xing, Jieyu
Lin, Limin
Li, Jing
Liu, Jiayu
Zhou, Changhua
Pan, Haitao
Shu, Rui
Dong, Bin
Cao, Donglin
Li, Qing
Wang, Zhong
BiHC, a T-Cell–Engaging Bispecific Recombinant Antibody, Has Potent Cytotoxic Activity Against Her2 Tumor Cells()
title BiHC, a T-Cell–Engaging Bispecific Recombinant Antibody, Has Potent Cytotoxic Activity Against Her2 Tumor Cells()
title_full BiHC, a T-Cell–Engaging Bispecific Recombinant Antibody, Has Potent Cytotoxic Activity Against Her2 Tumor Cells()
title_fullStr BiHC, a T-Cell–Engaging Bispecific Recombinant Antibody, Has Potent Cytotoxic Activity Against Her2 Tumor Cells()
title_full_unstemmed BiHC, a T-Cell–Engaging Bispecific Recombinant Antibody, Has Potent Cytotoxic Activity Against Her2 Tumor Cells()
title_short BiHC, a T-Cell–Engaging Bispecific Recombinant Antibody, Has Potent Cytotoxic Activity Against Her2 Tumor Cells()
title_sort bihc, a t-cell–engaging bispecific recombinant antibody, has potent cytotoxic activity against her2 tumor cells()
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548338/
https://www.ncbi.nlm.nih.gov/pubmed/28797938
http://dx.doi.org/10.1016/j.tranon.2017.07.003
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