Discovery Oncology, Roche Pharma Research and Early Development pRED, Roche Glycart AG, Schlieren, Switzerland.
MAbs. 2012 Nov-Dec;4(6):653-63. doi: 10.4161/mabs.21379. Epub 2012 Aug 27.
The development of bispecific antibodies has attracted substantial interest, and many different formats have been described. Those specifically containing an Fc part are mostly tetravalent, such as stabilized IgG-scFv fusions or dual-variable domain (DVD) IgGs. However, although they exhibit IgG-like properties and technical developability, these formats differ in size and geometry from classical IgG antibodies. Thus, considerable efforts focus on bispecific heterodimeric IgG antibodies that more closely mimic natural IgG molecules. The inherent chain association problem encountered when producing bispecific heterodimeric IgG antibodies can be overcome by several methods. While technologies like knobs-into-holes (KiH) combined with a common light chain or the CrossMab technology enforce the correct chain association, other approaches, e.g., the dual-acting Fab (DAF) IgGs, do not rely on a heterodimeric Fc part. This review discusses the state of the art in bispecific heterodimeric IgG antibodies, with an emphasis on recent progress.
双特异性抗体的开发引起了广泛关注，已经描述了许多不同的形式。那些特别含有 Fc 部分的抗体大多是四价的，例如稳定化的 IgG-scFv 融合物或双可变结构域 (DVD) IgG。然而，尽管这些抗体具有 IgG 样性质和技术可开发性，但它们在大小和几何形状上与经典 IgG 抗体不同。因此，人们投入了相当大的精力来研究更能模拟天然 IgG 分子的双特异性异二聚体 IgG 抗体。在生产双特异性异二聚体 IgG 抗体时遇到的固有链缔合问题可以通过几种方法来克服。虽然像 Knobs-into-holes (KiH) 与通用轻链结合或 CrossMab 技术这样的技术可以强制正确的链缔合，但其他方法，例如双作用 Fab (DAF) IgG，则不依赖于异二聚体 Fc 部分。本文讨论了双特异性异二聚体 IgG 抗体的最新技术进展，重点介绍了最近的进展。
