Advances in Therapeutic Fc engineering - Modulation of igG-Associated effector Functions and Serum Half-life

doi:10.3389/fimmu.2016.00580

	Advances in Therapeutic Fc engineering - Modulation of igG-Associated effector Functions and Serum Half-life
	Saxena, Abhishek; Wu, Donghui
	2016-12-12
发表期刊	FRONTIERS IN IMMUNOLOGY
ISSN	1664-3224
卷号	7
发表状态	已发表
DOI	10.3389/fimmu.2016.00580
摘要	Today, monoclonal immunoglobulin gamma (IgG) antibodies have become a major option in cancer therapy especially for the patients with advanced or metastatic cancers. Efficacy of monoclonal antibodies (mAbs) is achieved through both its antigen-binding fragment (Fab) and crystallizable fragment (Fc). Fab can specifically recognize tumor-associated antigen (TAA) and thus modulate TAA-linked downstream signaling pathways that may lead to the inhibition of tumor growth, induction of tumor apoptosis, and differentiation. The Fc region can further improve mAbs' efficacy by mediating effector functions such as antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cell-mediated phagocytosis. Moreover, Fc is the region interacting with the neonatal Fc receptor in a pH-dependent manner that can slow down IgG's degradation and extend its serum half-life. Loss of the antibody Fc region dramatically shortens its serum half-life and weakens its anticancer effects. Given the essential roles that the Fc region plays in the modulation of the efficacy of mAb in cancer treatment, Fc engineering has been extensively studied in the past years. This review focuses on the recent advances in therapeutic Fc engineering that modulates its related effector functions and serum half-life. We also discuss the progress made in aglycosylated mAb development that may substantially reduce the cost of manufacture but maintain similar efficacies as conventional glycosylated mAb. Finally, we highlight several Fc engineering- based mAbs under clinical trials.
关键词	antibody Fc region ADCC CDC ADCP serum half-life aglycosylated antibody FcRn cancer therapy
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[81572698]
WOS研究方向	Immunology
WOS类目	Immunology
WOS记录号	WOS:000389855600001
出版者	FRONTIERS MEDIA SA
WOS关键词	I-RELATED RECEPTOR ; ANTIBODY-BASED THERAPEUTICS ; AMINO-ACID-RESIDUES ; GAMMA-RIIA AFFINITY ; B-CELL RECEPTOR ; MONOCLONAL-ANTIBODY ; CRYSTAL-STRUCTURE ; ANTITUMOR-ACTIVITY ; BINDING-SITE ; CONFORMATIONAL STABILITY
原始文献类型	Review
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1603
专题	免疫化学研究所_特聘教授组_功能筛选实验室免疫化学研究所_特聘教授组_抗体工程学实验室
通讯作者	Wu, Donghui
作者单位	ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Lab Antibody Engn, Shanghai, Peoples R China
第一作者单位	免疫化学研究所
通讯作者单位	免疫化学研究所
第一作者的第一单位	免疫化学研究所
推荐引用方式 GB/T 7714	Saxena, Abhishek,Wu, Donghui. Advances in Therapeutic Fc engineering - Modulation of igG-Associated effector Functions and Serum Half-life[J]. FRONTIERS IN IMMUNOLOGY,2016,7.
APA	Saxena, Abhishek,&Wu, Donghui.(2016).Advances in Therapeutic Fc engineering - Modulation of igG-Associated effector Functions and Serum Half-life.FRONTIERS IN IMMUNOLOGY,7.
MLA	Saxena, Abhishek,et al."Advances in Therapeutic Fc engineering - Modulation of igG-Associated effector Functions and Serum Half-life".FRONTIERS IN IMMUNOLOGY 7(2016).