Gerber Hans-Peter, Senter Peter D, Grewal Iqbal S
Department of Pre-Clinical Therapeutics, Seattle Genetics, Inc., Bothell, WA 98021, USA.
MAbs. 2009 May-Jun;1(3):247-53. doi: 10.4161/mabs.1.3.8515.
Reducing the blood supply of tumors is one modality to combat cancer. Monoclonal antibodies are now established as a key therapeutic approach for a range of diseases. Owing to the ability of antibodies to selectively target endothelial cells within the tumor vasculature, vascular targeting programs have become a mainstay in oncology drug development. However, the antitumor activity of single agent administration of conventional anti-angiogenic compounds is limited and the improvements in patient survival are most prominent in combinations with chemotherapy. Furthermore, prolonged treatment with conventional anti-angiogenic drugs is associated with toxicity and drug resistance. These circumstances provide a strong rationale for novel approaches to enhance the efficacy of mAbs targeting tumor vasculature such as antibody-drug conjugates (ADCs).Here, we review trends in the development of ADCs targeting tumor vasculature with the aim of informing future research and development of this class of therapeutics.
减少肿瘤的血液供应是对抗癌症的一种方式。单克隆抗体现已成为一系列疾病的关键治疗方法。由于抗体能够选择性地靶向肿瘤脉管系统内的内皮细胞,血管靶向方案已成为肿瘤学药物开发的主要支柱。然而,传统抗血管生成化合物单药给药的抗肿瘤活性有限,与化疗联合使用时患者生存率的提高最为显著。此外,长期使用传统抗血管生成药物会产生毒性和耐药性。这些情况为增强靶向肿瘤脉管系统的单克隆抗体(如抗体-药物偶联物(ADC))疗效的新方法提供了有力的理论依据。在此,我们综述了靶向肿瘤脉管系统的ADC的发展趋势,旨在为这类治疗药物的未来研发提供参考。