Division of Early Drug Development for Innovative Therapy, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy.
Department of Oncology and Haematology (DIPO), University of Milan, Milan, Italy.
J Hematol Oncol. 2021 Jan 28;14(1):20. doi: 10.1186/s13045-021-01035-z.
Antibody-drug conjugates (ADCs) are a relatively new class of anticancer agents designed to merge the selectivity of monoclonal antibodies with cell killing properties of chemotherapy. They are commonly described as the "Trojan Horses" of therapeutic armamentarium, because of their capability of directly conveying cytotoxic drug (payloads) into the tumor space, thus transforming chemotherapy into a targeted agent. Three novel ADCs have been recently approved, i.e., trastuzumab deruxtecan, sacituzumab govitecan and enfortumab vedotin, respectively, targeting HER2, Trop2 and Nectin4. Thanks to progressive advances in engineering technologies these drugs rely on, the spectrum of diseases sensitive to these drugs as well as their indications are in continuous expansion. Several novel ADCs are under evaluation, exploring new potential targets along with innovative payloads. This review aims at providing a summary of the technology behind these compounds and at presenting the latest ADCs approved in solid tumors, as well as at describing novel targets for ADCs under investigation and new strategies to optimize their efficacy in solid tumors.
抗体偶联药物（ADCs）是一类新型的抗癌药物，旨在将单克隆抗体的选择性与化疗的细胞杀伤特性相结合。由于其能够将细胞毒性药物（有效载荷）直接输送到肿瘤部位，从而将化疗转化为靶向药物，因此它们通常被描述为治疗武器库中的“特洛伊木马”。最近有三种新型 ADC 获批，分别为靶向 HER2 的曲妥珠单抗 deruxtecan、靶向 Trop2 的 sacituzumab govitecan 和靶向 Nectin4 的 enfortumab vedotin。得益于其所依赖的工程技术的不断进步，这些药物敏感的疾病谱及其适应证正在不断扩大。目前正在评估几种新型 ADC，它们正在探索新的潜在靶点和创新的有效载荷。本文旨在总结这些化合物背后的技术，并介绍已在实体瘤中获批的最新 ADC，同时描述正在研究的 ADC 的新靶点和优化其在实体瘤中疗效的新策略。
