Cell Chemical Biology ( IF 6.6 ) Pub Date : 2024-08-06 , DOI: 10.1016/j.chembiol.2024.07.004 Rob C Oslund 1 , Pamela M Holland 2 , Scott A Lesley 2 , Olugbeminiyi O Fadeyi 1
The growing clinical success of bispecific antibodies (bsAbs) has led to rapid interest in leveraging dual targeting in order to generate novel modes of therapeutic action beyond mono-targeting approaches. While bsAbs that bind targets on two different cells (trans-targeting) are showing promise in the clinic, the co-targeting of two proteins on the same cell surface through cis-targeting bsAbs (cis-bsAbs) is an emerging strategy to elicit new functionalities. This includes the ability to induce proximity, enhance binding to a target, increase target/cell selectivity, and/or co-modulate function on the cell surface with the goal of altering, reversing, or eradicating abnormal cellular activity that contributes to disease. In this review, we focus on the impact of cis-bsAbs in the clinic, their emerging applications, and untangle the intricacies of improving bsAb discovery and development.
中文翻译:
顺式靶向双特异性抗体的治疗潜力
双特异性抗体(bsAb)在临床上的不断成功引起了人们对利用双重靶向产生超越单靶向方法的新治疗作用模式的兴趣。虽然结合两个不同细胞上的靶点(反式靶向)的 bsAb 在临床上显示出前景,但通过顺式靶向 bsAb( cis -bsAbs)共同靶向同一细胞表面上的两种蛋白质是一种新兴策略,可引发新的研究。功能。这包括诱导接近、增强与靶标的结合、增加靶标/细胞选择性和/或共调节细胞表面功能的能力,其目的是改变、逆转或消除导致疾病的异常细胞活动。在这篇综述中,我们重点关注顺式bsAb 在临床中的影响及其新兴应用,并阐明改善 bsAb 发现和开发的复杂性。