Department of Chemical Engineering, Pukyong National University, Yongso-ro 45, Nam-gu, Busan, South Korea.
Pharmacol Ther. 2020 Aug;212:107582. doi: 10.1016/j.pharmthera.2020.107582. Epub 2020 May 23.
Bispecific therapeutics target two distinct antigens simultaneously and provide novel functionalities that are not attainable with single monospecific molecules or combinations of them. The unique potential of bispecific therapeutics is driving extensive efforts to discover synergistic dual targets, design molecular formats to integrate bispecific elements, and accelerate successful clinical translation. In particular, the past decade has witnessed a boom in the design and development of bispecific antibody formats with more than 100 collections to date. Despite the remarkable progress that has been made to expand the number of formats, qualitative fine-tuning of bispecific formats is needed to achieve optimal dual-target engagement based on understanding of the spatiotemporal interdependence of the two physically linked binding specificities and the complex target biology associated with bispecific approaches. This review provides insights into the design parameters - including affinity, valency, and geometry - that need to be considered at an early stage of development in order to take the best advantage of bispecific therapeutics.
双特异性治疗药物同时针对两个不同的抗原，并提供了单克隆特异性分子或其组合无法实现的新功能。双特异性治疗药物的独特潜力正在推动广泛的努力，以发现协同的双重靶标，设计分子形式来整合双特异性元件，并加速成功的临床转化。特别是，在过去的十年中，双特异性抗体形式的设计和开发蓬勃发展，迄今为止已有超过 100 种组合。尽管在扩大格式数量方面取得了显著进展，但需要对双特异性格式进行定性微调，以根据对两个物理连接的结合特异性的时空相关性以及与双特异性方法相关的复杂靶标生物学的理解，实现最佳的双重靶标结合。本综述提供了设计参数的见解，包括亲和力、价态和几何形状，这些参数需要在开发的早期阶段考虑，以充分利用双特异性治疗药物。
