| Item type |
文献 / Documents(1) |
| 公開日 |
2021-08-26 |
| アクセス権 |
|
|
アクセス権 |
open access |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1038/s41598-020-61840-3 |
|
|
言語 |
ja |
|
|
関連名称 |
10.1038/s41598-020-61840-3 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
Build-up functionalization of anti-EGFR × anti-CD3 bispecific diabodies by integrating high-affinity mutants and functional molecular formats |
|
言語 |
en |
| 著者 |
アサノ, リュウタロウ
ホソカワ, カツヒロ
タキ, シンタロウ
コンノ, ショウタ
シモムラ, イッペイ
オガタ, ヒロミ
オカダ, マイ
アライ, キョウコ
鬼塚, 正義
大政, 健史
ナカニシ, タケシ
ウメツ, ミツオ
クマガイ, イズミ
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
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. |
|
言語 |
en |
| 書誌情報 |
en : Scientific Reports
巻 10,
p. 4913,
発行日 2020-03-18
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
20452322 |
| 出版者 |
|
|
出版者 |
Springer Nature |
|
言語 |
en |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
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/. |
| EID |
|
|
識別子 |
373147 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
srep_10_4913.pdf (2.75 MB)
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