A semi high-throughput method for screening small bispecific antibodies with high cytotoxicity

Abstract Small bispecific antibodies that induce T-cell–mediated cytotoxicity have the potential to damage late-stage tumor masses to a clinically relevant degree, but their cytotoxicity is critically dependent on their structural and functional properties. Here, we constructed an optimized procedur...

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Autores principales:	Aruto Sugiyama, Mitsuo Umetsu, Hikaru Nakazawa, Teppei Niide, Tomoko Onodera, Katsuhiro Hosokawa, Shuhei Hattori, Ryutaro Asano, Izumi Kumagai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f18cb9ec074743a0b52efdd168550715
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spelling	oai:doaj.org-article:f18cb9ec074743a0b52efdd1685507152021-12-02T11:52:44ZA semi high-throughput method for screening small bispecific antibodies with high cytotoxicity10.1038/s41598-017-03101-42045-2322https://doaj.org/article/f18cb9ec074743a0b52efdd1685507152017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03101-4https://doaj.org/toc/2045-2322Abstract Small bispecific antibodies that induce T-cell–mediated cytotoxicity have the potential to damage late-stage tumor masses to a clinically relevant degree, but their cytotoxicity is critically dependent on their structural and functional properties. Here, we constructed an optimized procedure for identifying highly cytotoxic antibodies from a variety of the T-cell–recruiting antibodies engineered from a series of antibodies against cancer antigens of epidermal growth factor receptor family and T-cell receptors. By developing and applying a set of rapid operations for expression vector construction and protein preparation, we screened the cytotoxicity of 104 small antibodies with diabody format and identified some with 103-times higher cytotoxicity than that of previously reported active diabody. The results demonstrate that cytotoxicity is enhanced by synergistic effects between the target, epitope, binding affinity, and the order of heavy-chain and light-chain variable domains. We demonstrate the importance of screening to determine the critical rules for highly cytotoxic antibodies.Aruto SugiyamaMitsuo UmetsuHikaru NakazawaTeppei NiideTomoko OnoderaKatsuhiro HosokawaShuhei HattoriRyutaro AsanoIzumi KumagaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aruto Sugiyama Mitsuo Umetsu Hikaru Nakazawa Teppei Niide Tomoko Onodera Katsuhiro Hosokawa Shuhei Hattori Ryutaro Asano Izumi Kumagai A semi high-throughput method for screening small bispecific antibodies with high cytotoxicity
description	Abstract Small bispecific antibodies that induce T-cell–mediated cytotoxicity have the potential to damage late-stage tumor masses to a clinically relevant degree, but their cytotoxicity is critically dependent on their structural and functional properties. Here, we constructed an optimized procedure for identifying highly cytotoxic antibodies from a variety of the T-cell–recruiting antibodies engineered from a series of antibodies against cancer antigens of epidermal growth factor receptor family and T-cell receptors. By developing and applying a set of rapid operations for expression vector construction and protein preparation, we screened the cytotoxicity of 104 small antibodies with diabody format and identified some with 103-times higher cytotoxicity than that of previously reported active diabody. The results demonstrate that cytotoxicity is enhanced by synergistic effects between the target, epitope, binding affinity, and the order of heavy-chain and light-chain variable domains. We demonstrate the importance of screening to determine the critical rules for highly cytotoxic antibodies.
format	article
author	Aruto Sugiyama Mitsuo Umetsu Hikaru Nakazawa Teppei Niide Tomoko Onodera Katsuhiro Hosokawa Shuhei Hattori Ryutaro Asano Izumi Kumagai
author_facet	Aruto Sugiyama Mitsuo Umetsu Hikaru Nakazawa Teppei Niide Tomoko Onodera Katsuhiro Hosokawa Shuhei Hattori Ryutaro Asano Izumi Kumagai
author_sort	Aruto Sugiyama
title	A semi high-throughput method for screening small bispecific antibodies with high cytotoxicity
title_short	A semi high-throughput method for screening small bispecific antibodies with high cytotoxicity
title_full	A semi high-throughput method for screening small bispecific antibodies with high cytotoxicity
title_fullStr	A semi high-throughput method for screening small bispecific antibodies with high cytotoxicity
title_full_unstemmed	A semi high-throughput method for screening small bispecific antibodies with high cytotoxicity
title_sort	semi high-throughput method for screening small bispecific antibodies with high cytotoxicity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f18cb9ec074743a0b52efdd168550715
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A semi high-throughput method for screening small bispecific antibodies with high cytotoxicity

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