Roche Innovation Center Zurich, Schlieren, Switzerland.
Roche Innovation Center Munich, Penzberg, Germany.
MAbs. 2021 Jan-Dec;13(1):1967714. doi: 10.1080/19420862.2021.1967714.
Bispecific antibodies have recently attracted intense interest. CrossMab technology was described in 2011 as novel approach enabling correct antibody light-chain association with their respective heavy chain in bispecific antibodies, together with methods enabling correct heavy-chain association using existing pairs of antibodies. Since the original description, CrossMab technology has evolved in the past decade into one of the most mature, versatile, and broadly applied technologies in the field, and nearly 20 bispecific antibodies based on CrossMab technology developed by Roche and others have entered clinical trials. The most advanced of these are the Ang-2/VEGF bispecific antibody faricimab, currently undergoing regulatory review, and the CD20/CD3 T cell bispecific antibody glofitamab, currently in pivotal Phase 3 trials. In this review, we introduce the principles of CrossMab technology, including its application for the generation of bi-/multispecific antibodies with different geometries and mechanisms of action, and provide an overview of CrossMab-based therapeutics in clinical trials.
双特异性抗体最近引起了广泛关注。2011 年，CrossMab 技术被描述为一种新方法，能够使双特异性抗体中的正确抗体轻链与其各自的重链结合，同时还提供了使用现有抗体对正确重链进行结合的方法。自最初描述以来，CrossMab 技术在过去十年中发展成为该领域最成熟、用途最广泛、应用最广泛的技术之一，罗氏等公司基于 CrossMab 技术开发的近 20 种双特异性抗体已进入临床试验。其中最先进的是 Ang-2/VEGF 双特异性抗体 faricimab，目前正在进行监管审查，以及 CD20/CD3 T 细胞双特异性抗体 glofitamab，目前正在进行关键的 3 期临床试验。在这篇综述中，我们介绍了 CrossMab 技术的原理，包括其在生成具有不同几何形状和作用机制的双-/多特异性抗体中的应用，并概述了临床试验中的 CrossMab 疗法。
