Structure of the Fab fragment of therapeutic antibody Ofatumumab provides insights into the recognition mechanism with CD20

	Structure of the Fab fragment of therapeutic antibody Ofatumumab provides insights into the recognition mechanism with CD20
	Du, JM; Yang, H; Guo, YJ; Ding, JP
刊名	MOLECULAR IMMUNOLOGY
	2009
卷号	46 期号:1 页码:2419-2423
关键词	CD20 Ofatumumab 2F2 Therapeutic antibody Crystal structure
通讯作者	Guo, YJ (reprint author), Second Mil Med Univ, Int Joint Canc Inst, 800 Xiang Yin Rd, Shanghai 200433, Peoples R China.,yjguo@smmu.edu.cn
英文摘要	CD20 is an important drug target for B-cell depletion therapy against certain B-cell lymphomas and autoimmune diseases. The success of anti-CD20 antibody drugs such as Rituximab, Ibritumomab, and Tositumomab has promoted the development of new generation of anti-CD20 antibodies for therapeutic applications. Ofatumumab is a fully human anti-CD20 antibody that is currently in phase III clinical trial for several types of malignancies and autoimmune diseases and is one of the most promising anti-CD20 drugs. Here we report the crystal structure of the Fab fragment of Ofatumumab at 2.2 angstrom resolution. The antigen combining site is composed of a large, deep pocket formed by six CDR loops. The pocket has a hydrophobic periphery and a positively charged bottom. Structure analysis and comparison with other antibodies suggest that the hydrophobic periphery might interact with the epitope on CD20 that is enriched with hydrophobic residues and very close to cell membrane, and the positively charged bottom might interact with Glu(150) of CD20 which is the only negatively charged residue within the epitope. These results provide some insights into the recognition of Ofatumumab with CD20 and explain how the antibody can recognize an epitope so close to the cell membrane. (C) 2009 Elsevier Ltd. All rights reserved.
学科主题	Biochemistry & Molecular Biology ; Immunology
类目[WOS]	Biochemistry & Molecular Biology ; Immunology
关键词[WOS]	ANTI-CD20 MONOCLONAL-ANTIBODY ; B-LYMPHOCYTES ; FINE SPECIFICITY ; HIV ANTIBODY ; CLINICAL-USE ; RITUXIMAB ; LYMPHOMAS ; EPITOPES ; EFFICACY ; COMPLEX
收录类别	SCI
语种	英语
WOS记录号	WOS:000267685700033
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1307]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Du, JM,Yang, H,Guo, YJ,et al. Structure of the Fab fragment of therapeutic antibody Ofatumumab provides insights into the recognition mechanism with CD20[J]. MOLECULAR IMMUNOLOGY,2009,46(1):2419-2423.
APA	Du, JM,Yang, H,Guo, YJ,&Ding, JP.(2009).Structure of the Fab fragment of therapeutic antibody Ofatumumab provides insights into the recognition mechanism with CD20.MOLECULAR IMMUNOLOGY,46(1),2419-2423.
MLA	Du, JM,et al."Structure of the Fab fragment of therapeutic antibody Ofatumumab provides insights into the recognition mechanism with CD20".MOLECULAR IMMUNOLOGY 46.1(2009):2419-2423.