A new approach to produce IgG(4)-like bispecific antibodies

doi:10.1038/s41598-021-97393-2

	A new approach to produce IgG(4)-like bispecific antibodies
	Zhao, Caizhi 1,2; Zhang, Wei 2; Gong, Guihua 2; Xie, Liping 2; Wang, Ming-Wei 1,3; Hu, Youjia 2
刊名	SCIENTIFIC REPORTS
	2021-09-20
卷号	11 期号:1 页码:12
ISSN号	2045-2322
DOI	10.1038/s41598-021-97393-2
通讯作者	Wang, Ming-Wei(mwwang@simm.ac.cn) ; Hu, Youjia(huyoujia@sinopharm.com)
英文摘要	While achieving rapid developments in recent years, bispecific antibodies are still difficult to design and manufacture, due to mispair of both heavy and light chains. Here we report a novel technology to make bispecific molecules. The knob-into-hole method was used to pair two distinct heavy chains as a heterodimer. IgG(4) S228P CH1-CL interface was then partially replaced by T-cell receptor alpha/beta constant domain to increase the efficiency of cognate heavy and light chain pairing. Following expression and purification, the bispecific antibody interface exchange was confirmed by Western blotting and LC-MS/MS. To ensure its validity, we combined a monovalent bispecific antibody against PD-1 (sequence from Pembrolizumab) and LAG3 (sequence from Relatlimab). The results showed that the molecule could be assembled correctly at a ratio of 95% in cells. In vitro functional assay demonstrated that the purified bispecific antibody exhibits an enhanced agonist activity compared to that of the parental antibodies. Low immunogenicity was predicted by an open-access software and ADA test.
资助项目	Shanghai Municipal Education Commission (Shanghai Top-Level University Capacity Building Program)[DGF817029-04]
WOS关键词	DOMAIN INTERFACE ; REGULATORY T ; RECEPTOR ; BLOCKADE ; PD-1 ; HETERODIMERS ; EXPRESSION ; MOLECULES ; PLATFORM ; DESIGN
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PORTFOLIO
WOS记录号	WOS:000700289800024
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297463]
专题	中国科学院上海药物研究所
通讯作者	Wang, Ming-Wei; Hu, Youjia
作者单位	1.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China 2.China State Inst Pharmaceut Ind, Shanghai 201203, Peoples R China 3.Natl Ctr Drug Screening, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Caizhi,Zhang, Wei,Gong, Guihua,et al. A new approach to produce IgG(4)-like bispecific antibodies[J]. SCIENTIFIC REPORTS,2021,11(1):12.
APA	Zhao, Caizhi,Zhang, Wei,Gong, Guihua,Xie, Liping,Wang, Ming-Wei,&Hu, Youjia.(2021).A new approach to produce IgG(4)-like bispecific antibodies.SCIENTIFIC REPORTS,11(1),12.
MLA	Zhao, Caizhi,et al."A new approach to produce IgG(4)-like bispecific antibodies".SCIENTIFIC REPORTS 11.1(2021):12.