双-多特异性纳米抗体的构建形式

双特异性抗体（双抗）可以同时特异性结合2种不同抗原，已成为抗体工程领域研究的热点。这些研究主要集中在癌症治疗方面，虽疗效显著但还未达到临床最佳状态。由于双抗有2条重链和2条轻链，因而极易出现错配。为解决这一问题，研究者设计出许多不同的双抗形式，例如串联单链抗体、双可变结构域抗体或使用“knobs-into-holes”方式构建的抗体，但仍不能得到最优的双抗。纳米抗体是目前已知最小的全功能抗体，具有许多优异的理化特性，为构建双-多特异性抗体提供了一种全新的途径。

Bi-and multi- specific nanobody construction formats

Bi-specific antibodies (BsAbs) recognizing two different antigens simultaneously have become hot spot in antibody engineering recently. Most BsAbs are developed for cancer immunotherapy but only sub-optimal effects have been achieved so far. The major bottlenecks for developing BsAb are the heavy and light chain pairing problems. Many alternative BsAb formats are explored for overcoming these problems, including  tandem single chain fragment variable, dual-variable domains-Ig and knobs-into-holes. Despite the extensive efforts, more robust formats remain highly need to construct better BsAbs. Heavy chain-only nanobodies are the smallest fully functional antibody and a novel building block for constructing bi- and multi-specific antibodies.