交叉反应性抗体结合来自不同物种的多个相关或不相关靶标的能力不仅提供了优异的治疗功效,而且还提供了更好的治疗毒性评估。从而促进从临床前模型到人类临床研究的过渡。本章为使用酵母表面展示技术的交叉反应性抗体的定向进化提供了一些指导。交叉反应性抗体最初通过组合高度狂热的磁珠分离,然后进行多个循环的流式细胞术分选,从初始文库中分离。一旦鉴定出最初的交叉反应性克隆,连续轮次的诱变和双压选择策略被应用于工程化交叉反应性抗体,具有改善的亲和力,但仍保留或优异的交叉反应性.
The ability of cross-reactive antibodies to bind multiple related or unrelated targets derived from different species provides not only superior therapeutic efficacy but also a better assessment of treatment toxicity, thereby facilitating the transition from preclinical models to human clinical studies. This chapter provides some
guidelines for the directed evolution of cross-reactive antibodies using yeast surface display technology. Cross-reactive antibodies are initially isolated from a naïve library by combining highly avid magnetic bead separations followed by multiple cycles of flow cytometry sorting. Once initial cross-reactive clones are identified, sequential rounds of mutagenesis and two-pressure selection strategies are applied to engineer cross-reactive antibodies with improved affinity and yet retained or superior cross-reactivity.