Borcoman Edith, Le Tourneau Christophe
aDepartment of Medical Oncology, Institut Curie, Paris & Saint-Cloud bEA7285, Versailles-Saint-Quentin-en-Yvelines University, Versailles, France.
Curr Opin Oncol. 2016 Sep;28(5):429-36. doi: 10.1097/CCO.0000000000000310.
The current review describes the rationale and current clinical development of antibody drug conjugates (ADCs), along with their perspectives for the future.
Trastuzumab emtansine was the first ADC approved by the U.S. Food and Drug Administration for the treatment of human epidermal growth factor receptor 2 positive metastatic breast cancer in the second-line setting, with a high efficacy and a favorable safety profile. ADC represents an exciting new class of cancer therapeutics that combines a targeted approach for delivering cytotoxic agents. About 30 new ADCs are currently under investigation in oncology.
ADCs are empowered antibodies designed to exploit the targeting ability of monoclonal antibodies (mAbs) by linking them to cytotoxic agents, giving them higher tumor selectivity, and potentially an increased therapeutic window, as compared with cytotoxic agents alone. The key components of ADCs include a mAb, a stable linker and a cytotoxic agent. In linking mAbs with cytotoxic agents, the aim is to optimize the properties of both components, bringing their complementary features together. Trastuzumab emtansine has been the first ADC to be marketed in human epidermal growth factor receptor 2 positive metastatic breast cancer. Current clinical development of ADCs includes a variety of targets, as well as combinations with other therapeutic agents, such as chemotherapy, radiotherapy, targeted therapies, and immune checkpoint inhibitors.
本综述描述了抗体药物偶联物(ADC)的原理和当前临床进展,以及它们的未来前景。
曲妥珠单抗-恩杂鲁胺是首个被美国食品药品监督管理局批准用于二线治疗人表皮生长因子受体2阳性转移性乳腺癌的ADC,具有高效和良好的安全性。ADC代表了一类令人兴奋的新型癌症治疗药物,它结合了一种靶向递送细胞毒性药物的方法。目前约有30种新的ADC正在肿瘤学领域进行研究。
ADC是一种经过改良的抗体,通过将其与细胞毒性药物连接,利用单克隆抗体(mAb)的靶向能力,与单独使用细胞毒性药物相比,使其具有更高的肿瘤选择性,并可能扩大治疗窗口。ADC的关键组成部分包括单克隆抗体、稳定的连接子和细胞毒性药物。将单克隆抗体与细胞毒性药物连接的目的是优化这两种成分的特性,使其互补特性结合在一起。曲妥珠单抗-恩杂鲁胺是首个在人表皮生长因子受体2阳性转移性乳腺癌中上市的ADC。ADC目前的临床开发包括多种靶点,以及与其他治疗药物的联合应用,如化疗、放疗、靶向治疗和免疫检查点抑制剂。