Jerjian Taleen V, Glode Ashley E, Thompson Lisa A, O'Bryant Cindy L
University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado.
Pharmacotherapy. 2016 Jan;36(1):99-116. doi: 10.1002/phar.1687.
Antibody-drug conjugates (ADCs) combine highly specific monoclonal antibodies with potent cytotoxic drugs. Their synergy allows for targeted delivery of toxic drugs to cancer cells while sparing systemic exposure. In this review, we focus on the history and clinical applications of ADCs approved by the U.S. Food and Drug Administration (FDA) for the treatment of cancer and highlight new ADCs in the drug development pipeline. Three ADCs have received FDA approval thus far. Gemtuzumab ozogamicin, although withdrawn from the U.S. market, may still be an effective treatment modality in subsets of patients with acute myeloid leukemia. Brentuximab vedotin and ado-trastuzumab emtansine have shown improved efficacy and safety data compared with standard chemotherapy for the treatment of advanced lymphoma and breast cancer, respectively. With a number of ADCs with promising preliminary data in the clinical trial pipeline, cancer therapy is moving forward from traditional chemotherapy to targeted treatment modalities driven by the specificity of monoclonal antibodies and advancing biotechnology.
抗体药物偶联物(ADCs)将高度特异性的单克隆抗体与强效细胞毒性药物结合在一起。它们的协同作用能够将有毒药物靶向递送至癌细胞,同时避免全身暴露。在本综述中,我们聚焦于美国食品药品监督管理局(FDA)批准用于癌症治疗的ADCs的历史及临床应用,并着重介绍处于药物研发阶段的新型ADCs。迄今为止,已有三款ADCs获得FDA批准。吉妥单抗奥唑米星尽管已从美国市场撤出,但对于部分急性髓系白血病患者而言可能仍是一种有效的治疗方式。与标准化疗相比,维布妥昔单抗和ado曲妥珠单抗 emtansine分别在晚期淋巴瘤和乳腺癌的治疗中显示出了更好的疗效和安全性数据。随着多款在临床试验中具有 promising 初步数据的ADCs的出现,癌症治疗正从传统化疗转向由单克隆抗体的特异性和不断发展的生物技术驱动的靶向治疗模式。