Fabs-in-tandem immunoglobulin is a novel and versatile bispecific design for engaging multiple therapeutic targets
Fabs-in-tandem immunoglobulin is a novel and versatile bispecific design for engaging multiple therapeutic targets
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DOI：
10.1080/19420862.2017.1345401
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发表时间：
2017-01-01
期刊：
影响因子：
5.3
通讯作者：
Wu, Chengbin
中科院分区：
文献类型：
--
作者：
Gong, Shiyong;Ren, Fang;Wu, Chengbin
近年来，双特异性抗体（bsAb）的开发已成为生物制药行业的一大趋势。通过同时作用于2个分子靶点，bsab显示出独特的作用机制，可能导致传统单克隆抗体无法达到的临床疗效。已经描述了各种bsAb生成格式，其中一些正在临床开发中进行研究。然而，由于其不利的物理化学和药代动力学性质以及较差的制造效率，一些bsAb结构已被证明是有问题的。我们在这里描述了一种新的双特异性设计，fab -in-tandem免疫球蛋白（FIT-Ig），其中2个抗原结合片段直接以交叉方向融合，而不需要任何突变或使用肽连接物。这种独特的设计提供了一个对称的类igg双特异性分子，具有正确的2组VH/VL对的关联。我们证明FIT-Ig分子具有良好的药物样特性，体外和体内功能，以及用于商业开发的制造效率。
In recent years, the development of bispecific antibody (bsAb) has become a major trend in the biopharmaceutical industry. By simultaneously engaging 2 molcular targets, bsAbs show unique mechanisms of action that could lead to clinical benefits unattainable by conventional monoclonal antibodies. Various bsAb generation formats have been described, and several are being investigated in clinical development. However, some bsAb constructs have proven to be problematic due to their unfavorable physicochemical and pharmacokinetic properties, as well as poor manufacturing efficiencies. We describe here a new bispecific design, Fabs-in-tandem immunoglobulin (FIT-Ig), in which 2 antigen-binding fragments are fused directly in a crisscross orientation without any mutations or use of peptide linkers. This unique design provides a symmetric IgG-like bispecific molecule with correct association of 2 sets of VH/VL pairs. We show that FIT-Ig molecules exhibit favorable drug-like properties, in vitro and in vivo functions, as well as manufacturing efficiency for commercial development.