ID | 115833 |
Author |
Asano, Ryutaro
Tohoku University|Tokyo University of Agriculture and Technology
Hosokawa, Katsuhiro
Tohoku University
Taki, Shintaro
Tohoku University
Konno, Shota
Tohoku University
Shimomura, Ippei
Tohoku University
Ogata, Hiromi
Tohoku University
Okada, Mai
Tohoku University
Arai, Kyoko
Tohoku University
Onitsuka, Masayoshi
Tokushima University
Tokushima University Educator and Researcher Directory
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Nakanishi, Takeshi
Tohoku University
Umetsu, Mitsuo
Tohoku University
Kumagai, Izumi
Tohoku University
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Content Type |
Journal Article
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Description | Designing non-natural antibody formats is a practical method for developing highly functional next-generation antibody drugs, particularly for improving the therapeutic efficacy of cancer treatments. One approach is constructing bispecific antibodies (bsAbs). We previously reported a functional humanized bispecific diabody (bsDb) that targeted epidermal growth factor receptor and CD3 (hEx3-Db). We enhanced its cytotoxicity by constructing an Fc fusion protein and rearranging order of the V domain. In this study, we created an additional functional bsAb, by integrating the molecular formats of bsAb and high-affinity mutants previously isolated by phage display in the form of Fv. Introducing the high-affinity mutations into bsDbs successfully increased their affinities and enhanced their cytotoxicity in vitro and in vivo. However, there were some limitations to affinity maturation of bsDb by integrating high-affinity Fv mutants, particularly in Fc-fused bsDb with intrinsic high affinity, because of their bivalency. The tetramers fractionated from the bsDb mutant exhibited the highest in vitro growth inhibition among the small bsAbs and was comparable to the in vivo anti-tumor effects of Fc-fused bsDbs. This molecule shows cost-efficient bacterial production and high therapeutic potential.
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Journal Title |
Scientific Reports
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ISSN | 20452322
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Publisher | Springer Nature
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Volume | 10
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Start Page | 4913
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Published Date | 2020-03-18
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Rights | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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language |
eng
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departments |
Bioscience and Bioindustry
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