Shan Khine Swe, Musleh Ud Din Saba, Dalal Shivani, Gonzalez Teresita, Dalal Misha, Ferraro Pablo, Hussein Atif, Vulfovich Michel
Memorial Health Care, Division of Hematology and Oncology, Pembroke Pines, FL 33028, USA.
Memorial Health Care, Division of Internal Medicine, Pembroke Pines, FL 33028, USA.
Int J Mol Sci. 2025 Jun 18;26(12):5838. doi: 10.3390/ijms26125838.
Bispecific antibodies (BsAbs) have shown potential in cancer treatment and have become a rapidly growing field in cancer immunotherapy. Unlike monoclonal antibodies with two identical binding sites, BsAbs simultaneously bind two distinct epitopes on the same or different antigens, allowing for a range of mechanisms of action, including engaging immune cells to kill cancer cells and blocking signaling pathways. Despite regulatory approvals for hematological malignancies in the last decade, their clinical success in solid malignancies has been lacking until recently. There are currently five BsAbs approved by the FDA in the United States for solid tumors-amivantamab, tarlatamab, tebentafusp, zanidatamab and zenocutuzumab-and two BsAbs approved in China-cadonilimab and ivonescimab. Currently, several BsAbs are under clinical development for solid tumors, but are mostly in early phase I and II trials. This review provides an overview of the basic mechanism of action of BsAbs, current FDA-approved BsAbs, and current BsAbs under clinical development, their challenges in clinical use, the management of toxicities, and future directions.
双特异性抗体（BsAbs）在癌症治疗中已显示出潜力，并已成为癌症免疫治疗中一个快速发展的领域。与具有两个相同结合位点的单克隆抗体不同，BsAbs同时结合同一或不同抗原上的两个不同表位，从而产生一系列作用机制，包括促使免疫细胞杀死癌细胞以及阻断信号通路。尽管在过去十年中BsAbs已获监管机构批准用于治疗血液系统恶性肿瘤，但直到最近它们在实体恶性肿瘤的临床应用中才取得成功。目前，美国食品药品监督管理局（FDA）已批准五种BsAbs用于实体瘤治疗，分别是氨武单抗、他拉塔单抗、替贝福斯、扎尼达单抗和泽诺库单抗，中国已批准两种BsAbs，分别是卡度尼利单抗和伊沃西单抗。目前，有几种BsAbs正在进行实体瘤的临床试验，但大多处于I期和II期早期试验阶段。本综述概述了BsAbs的基本作用机制、目前FDA批准的BsAbs、正在进行临床试验的BsAbs、它们在临床应用中的挑战、毒性管理以及未来发展方向。
