Department of Biologics Research, West Point, PA, USA.
MAbs. 2009 Nov-Dec;1(6):572-9. doi: 10.4161/mabs.1.6.10185.
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 isotype, 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.
抗体的 Fc 区域介导效应功能，如抗体依赖的细胞介导的细胞毒性（ADCC）和补体依赖的细胞毒性（CDC），并在抗体的体内半衰期中发挥关键作用。在设计抗体治疗药物时，有时希望抗体具有改变的 Fc 介导的特性。在“良性阻滞剂”抗体的情况下，通常希望减少或消除 ADCC 和 CDC 功能，同时保留其 PK 特征。在这里，我们报告了一种新型工程 IgG 同种型 IgG2m4，其 Fc 功能降低。IgG2m4 基于 IgG2 同种型，具有源自 IgG4 的四个关键氨基酸残基变化（H268Q、V309L、A330S 和 P331S）。在体外结合分析中，IgG2m4 抗体的补体和 Fcγ受体结合总体减少，同时在恒河猴中保持正常的体内血清半衰期。
