Reduction of circulating IgE and allergens by a pH-sensitive antibody with enhanced FcyRIIb binding

doi:10.1016/j.ymthe.2024.08.029

KMS > 免疫化学研究所

	Reduction of circulating IgE and allergens by a pH-sensitive antibody with enhanced FcyRIIb binding
	Li, Na 1,2; Gong, Nanxin 1,2,3; Duan, Baoxin 1,2; Zhang, Yongyan 1,2; Jian, Yi 1,2; Xu, Yanqin 1,2; Liu, Jinming 1,2; Wang, Xiaoqian 1,2; Zhang, Xiaoqi 1,2; Du, Mingjuan4 ; Zhou, Feilong 1,2; Zhao, Jiliang 1,2; Guan, Xiangchen 1,2; Peng, Xiangda 5; Wang, Sheng 5; Zhang, Hongkai1,2,4 ; Li, Xin 1,2
	2024-10-02
发表期刊	MOLECULAR THERAPY (IF:12.1[JCR-2023],11.8[5-Year])
ISSN	1525-0016
EISSN	1525-0024
卷号	32 期号:10
DOI	10.1016/j.ymthe.2024.08.029
摘要	Allergen-crosslinked IgE triggers allergy by interacting with its receptor on basophils and mast cells. The anti-IgE monoclonal antibody omalizumab can alleviate allergy by competing with the receptor for IgE binding. However, along with neutralization, omalizumab also inhibits IgE degradation, which is clinically associated with high-dose and total IgE accumulation problems. In this study, we have developed an IgE-eliminating antibody on the basis of omalizumab, which has pH-dependent Fabs and an Fc with high affinity for FcgRIIb. In mice, the antibody rapidly eliminated total serum IgE to baseline levels and caused lower free IgE levels than omalizumab. At low dosages, the antibody also exhibited favorable IgE elimination effects. In addition, the antibody can degrade the corresponding allergen with the removal of IgE, addressing the allergy from its source. Introduction of the M252Y/S254T/T256E (YTE) mutation into this antibody prolongs its serum half-life without reducing potency. Thus, this engineered antibody holds a promising therapeutic option for allergy patients. Mechanistic insights are also included in this study.
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收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China["82273843","82261138553"] ; The "Frontiers Science Center for New Organic Matter," Nankai University[63181206]
WOS研究方向	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
WOS类目	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental
WOS记录号	WOS:001389493200001
出版者	CELL PRESS
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/470988
专题	免疫化学研究所免疫化学研究所_特聘教授组_张宏恺组
通讯作者	Zhang, Hongkai; Li, Xin
作者单位	1.Nankai Univ, Coll Life Sci, 94 Weijin Rd, Tianjin 300071, Peoples R China 2.Nankai Univ, State Key Lab Med Chem Biol, 94 Weijin Rd, Tianjin 300071, Peoples R China 3.Hebei Univ, Inst Life Sci & Green Dev, Coll Life Sci, Baoding 071002, Peoples R China 4.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China 5.Shanghai Zelixir Biotech, Shanghai 200030, 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	Li, Na,Gong, Nanxin,Duan, Baoxin,et al. Reduction of circulating IgE and allergens by a pH-sensitive antibody with enhanced FcyRIIb binding[J]. MOLECULAR THERAPY,2024,32(10).
APA	Li, Na.,Gong, Nanxin.,Duan, Baoxin.,Zhang, Yongyan.,Jian, Yi.,...&Li, Xin.(2024).Reduction of circulating IgE and allergens by a pH-sensitive antibody with enhanced FcyRIIb binding.MOLECULAR THERAPY,32(10).
MLA	Li, Na,et al."Reduction of circulating IgE and allergens by a pH-sensitive antibody with enhanced FcyRIIb binding".MOLECULAR THERAPY 32.10(2024).