Nature Reviews Clinical Oncology ( IF 81.1 ) Pub Date : 2024-09-26 , DOI: 10.1038/s41571-024-00946-3 Claudia A. J. van Winkel, Frank R. Pierik, Adrienne H. Brouwers, Derk Jan A. de Groot, Elisabeth G. E. de Vries, Marjolijn N. Lub-de Hooge
Multispecific antibodies are engineered antibody derivatives that can bind to two or more distinct epitopes or antigens. Unlike mixtures of monospecific antibodies, the binding properties of multispecific antibodies enable two specific molecules to be physically linked, a characteristic with important applications in cancer therapy. The field of multispecific antibodies is highly dynamic and expanding rapidly; to date, 15 multispecific antibodies have been approved for clinical use, of which 11 were approved for oncological indications, and more than 100 new antibodies are currently in clinical development. Nevertheless, substantial challenges limit the applications of multispecific antibodies in cancer therapy, particularly inefficient targeting of solid tumours and substantial adverse effects. Both PET and single photon emission CT imaging can reveal the biodistribution and complex pharmacology of radiolabelled multispecific antibodies. This Review summarizes the insights obtained from preclinical and clinical molecular imaging studies of multispecific antibodies, focusing on their structural properties, such as molecular weight, shape, target specificity, affinity and avidity. The opportunities associated with use of molecular imaging studies to support the clinical development of multispecific antibody therapies are also highlighted.
中文翻译:
分子成像支持多特异性癌症抗体的开发
多特异性抗体是工程化抗体衍生物,可与两个或多个不同的表位或抗原结合。与单特异性抗体的混合物不同,多特异性抗体的结合特性使两个特异性分子能够物理连接,这一特性在癌症治疗中具有重要应用。多特异性抗体领域高度动态且发展迅速;迄今为止,已有 15 种多特异性抗体被批准用于临床,其中 11 种被批准用于肿瘤适应症,目前有 100 多种新抗体正在临床开发中。然而,重大挑战限制了多特异性抗体在癌症治疗中的应用,尤其是实体瘤的低效靶向和严重的不良反应。PET 和单光子发射 CT 成像都可以揭示放射性标记的多特异性抗体的生物分布和复杂的药理学。本文总结了从多特异性抗体的临床前和临床分子成像研究中获得的见解,重点介绍其结构特性,例如分子量、形状、靶标特异性、亲和力和亲和力。还强调了与使用分子成像研究支持多特异性抗体疗法的临床开发相关的机会。