IgG2m4, an engineered antibody isotype with reduced Fc function

被引：74

作者：

An, Zhiqiang ^{[1
]}

Forrest, Gail ^{[3
]}

Moore, Renee ^{[4
]}

Cukan, Michael ^{[4
]}

Haytko, Peter ^{[1
]}

Huang, Lingyi ^{[1
]}

Vitelli, Salvatore ^{[1
]}

Zhao, Jing Zhang ^{[1
]}

Lu, Ping ^{[1
]}

Hua, Jin ^{[1
]}

Gibson, Christopher R. ^{[2
]}

Harvey, Barrett R. ^{[1
]}

Montgomery, Donna ^{[1
]}

Zaller, Dennis ^{[3
]}

Wang, Fubao ^{[1
]}

Strohl, William ^{[1
]}

机构：

[1] Dept Biol Res, West Point, PA USA

[2] Dept Drug Metab & Pharmacokinet, West Point, PA USA

[3] Merck & Co Inc, Merck Sharp & Dohme Res Labs, Dept Immunol, Rahway, NJ 07065 USA

[4] Merck & Co Inc, GlycoFi, Lebanon, NH USA

来源：

MABS | 2009年 / 1卷 / 06期

关键词：

IgG2m4; IgG; isotype; benign blocker; Fc gamma receptors; C1q; HUMAN-IMMUNOGLOBULIN-G; BINDING-SITE; GAMMA-RIIA; HUMAN IGG1; DIFFERENTIAL ABILITY; ACTIVATE COMPLEMENT; MONOCLONAL-ANTIBODY; EFFECTOR FUNCTIONS; RECEPTOR-IIA; CH2; DOMAIN;

D O I：

10.4161/mabs.1.6.10185

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The Fc region of an antibody mediates effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), and plays a key role in the in vivo half-life of an antibody. In designing antibody therapeutics, it is sometimes desirable that the antibody has altered Fc-mediated properties. In the case of a "benign blocker" antibody, it is often desirable to diminish or abolish the ADCC and CDC functions while retaining its PK profile. Here, we report a novel engineered IgG iscitype, IgG2m4, with reduced Fc functionality. IgG2m4 is based on the IgG2 isotype with four key amino acid residue changes derived from IgG4 (H268Q, V309L, A330S and P331S). An IgG2m4 antibody has an overall reduction in complement and Fc gamma receptor binding in in vitro binding analyses while maintaining the normal in vivo serum half-life in rhesus.

引用

页码：572 / 579

页数：8

共 43 条

[1] IgG4 breaking the rules [J].