Self-assembly of X-shaped antibody to combine the activity of IgG and IgA for enhanced tumor killing

doi:10.7150/thno.74903

	Self-assembly of X-shaped antibody to combine the activity of IgG and IgA for enhanced tumor killing
	Liang, Yuexi 1,2,3; Li, Xin 1,2,3; Peng, Fengping 5; Ye, Xiaohan 1,2,3; Wang, Wei4 ; Cen, Tianyi 1,2,3; Li, Fan 1,2,3; Lu, Yue 1,2; Liu, Zhaoyun 5; Liu, Hui 5; Ding, Kai 5; Ye, Kai 1,2,3; Yu, Yang 1,2,3; Ma, Tianyu 1,2,3; Zhang, Sihe 6; Huang, Yi 7; Wang, Yuan 1,2,3; Yang, Xue 1,2; Fu, Rong 5; Zhang, Hongkai1,2,3,4
	2022
发表期刊	THERANOSTICS
ISSN	1838-7640
卷号	12 期号:18
发表状态	已发表
DOI	10.7150/thno.74903
摘要	Rationale: IgA can induce activation of neutrophils which are the most abundant cell type in blood, but the development of IgA as therapeutic has been confounded by its short half-life and a weak ability to recruit NK cells as effector cells. Therefore, we generated an X-shaped antibody (X-body) based on the principle of molecular self-assembly that combines the activities of both IgG and IgA, which can effectively recruit and activate NK cells, macrophages, and neutrophils to kill tumor cells.Methods: X-body was generated by using a self-assembly strategy. The affinity of the X-body with the antigen and Fc receptors was tested by surface plasmon resonance. The shape of X-body was examined using negative staining transmission electron microscopy. The tumor cell killing activity of X-body was assessed in vitro and in multiple syngeneic mouse models. To explore the mechanism of X-body, tumor-infiltrating immune cells were analyzed by single-cell RNA-seq and flow cytometry. The dependence of neutrophil, macrophage, and NK cells for the X-body efficacy was confirmed by in vivo depletion of immune cell subsets.Results: The X-body versions of rituximab and trastuzumab combined the full spectrum activity of IgG and IgA and recruited NK cells, macrophages, and neutrophils as effector cells for eradication of tumor cells. Treatment with anti-hCD20 and anti-hHER2 X-bodies leads to a greater reduction in tumor burden in tumor-bearing mice compared with the IgA or IgG counterpart, and no obvious adverse effect is observed upon X-body treatment. Moreover, the X-body has a serum half-life and drug stability comparable to IgG. Conclusions: The X-body, as a myeloid-cell-centered therapeutic strategy, holds promise for the development of more effective cancer-targeting therapies than the current state of the art.
关键词	IgA IgG X-body self-assembly tumor-infiltrating neutrophil
URL	查看原文
收录类别	SCI
语种	英语
资助项目	National Key Research and Development plan of China[2018YFE0200400] ; National Natural Science Foundation of China[8227 3843] ; Key Research Fund of Tianjin Project Team[XB202010] ; Natural Science Foundation of Tianjin[19JCZDJC 32900] ; Tianjin Science and Technology Planning Project[20YFZCSY00060] ; Key Research and Development Program of Tianjin[20YFZCSY00450] ; Tianjin Municipal Health Commission Youth Project[TJWJ2021QN001]
WOS研究方向	Research & Experimental Medicine
WOS类目	Medicine, Research & Experimental
WOS记录号	WOS:000891576100006
出版者	IVYSPRING INT PUBL
引用统计	被引频次：4[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/266592
专题	免疫化学研究所_特聘教授组_张宏恺组免疫化学研究所_公共科研平台_生物医学大数据平台
通讯作者	Fu, Rong; Zhang, Hongkai
作者单位	1.Nankai Univ, State Key Lab Med Chem Biol, Tianjin 300350, Peoples R China 2.Nankai Univ, Coll Life Sci, Tianjin 300350, Peoples R China 3.Nankai Univ, Frontiers Sci Ctr Cell Responses, Tianjin 300350, Peoples R China 4.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China 5.Tianjin Med Univ, Dept Hematol, Gen Hosp, Tianjin 300052, Peoples R China 6.Nankai Univ, Sch Med, Dept Cell Biol, Tianjin 300350, Peoples R China 7.Shanghai Tanshi Biotechnol Co, Shanghai 201206, Peoples R China
通讯作者单位	免疫化学研究所
推荐引用方式 GB/T 7714	Liang, Yuexi,Li, Xin,Peng, Fengping,et al. Self-assembly of X-shaped antibody to combine the activity of IgG and IgA for enhanced tumor killing[J]. THERANOSTICS,2022,12(18).
APA	Liang, Yuexi.,Li, Xin.,Peng, Fengping.,Ye, Xiaohan.,Wang, Wei.,...&Zhang, Hongkai.(2022).Self-assembly of X-shaped antibody to combine the activity of IgG and IgA for enhanced tumor killing.THERANOSTICS,12(18).
MLA	Liang, Yuexi,et al."Self-assembly of X-shaped antibody to combine the activity of IgG and IgA for enhanced tumor killing".THERANOSTICS 12.18(2022).