Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California, USA.
Curr Opin Obstet Gynecol. 2019 Feb;31(1):18-23. doi: 10.1097/GCO.0000000000000515.
Antibody drug conjugates (ADC) are a novel class of cancer therapeutics, delivering cytotoxic therapy directly to cancer cells, and show promise in the management of platinum-resistant ovarian cancer. Herein we summarize the ADC landscape currently in clinical study.
Mirvetuximab Soravtansine, IMGN853, is an ADC targeting the folate receptor alpha (FRα) and has demonstrated promising single agent activity and a favorable toxicity profile in FRα-positive, platinum-resistant, epithelial ovarian cancer (EOC). The antitumor effect is seen primarily in less heavily pretreated EOC patients with moderate-to-high FRα tumor expression. A phase III study, randomizing patients to either IMGN853 or the physician's choice of single-agent chemotherapy has completed accrual. Additional ADC are being evaluated in ovarian cancer including agents that target NaPiB2, Trop2, mesothelin, and MUC16 are in phase 1 clinical trials.
ADC bind antigens overexpressed on cancer cells and provide site-selective drug delivery, with the goal to increase therapeutic efficacy of cytotoxics while decreasing the off-target toxicity of the payloads. With appropriate antigen selection and adequate, measurable antigen threshold targets, these new agents may provide an improved strategy for overcoming resistance to standard chemotherapy in ovarian cancer.
抗体药物偶联物（ADC）是一类新型的癌症治疗药物，可将细胞毒性疗法直接递送至癌细胞，在铂耐药卵巢癌的治疗中具有广阔的应用前景。本文总结了目前正在临床研究中的 ADC 领域的相关进展。
靶向叶酸受体-α（FRα）的 ADC 药物 Mirvetuximab Soravtansine（IMGN853）在 FRα 阳性、铂耐药的上皮性卵巢癌（EOC）患者中显示出单药治疗的良好活性和可接受的毒性特征。其抗肿瘤作用主要见于 FRα 肿瘤表达中等到高度、预处理较少的 EOC 患者中。一项将患者随机分配至 IMGN853 或医生选择的单药化疗的 III 期研究已完成入组。其他 ADC 药物也正在卵巢癌中进行评估，包括靶向 NaPiB2、Trop2、间皮素和 MUC16 的药物正在进行 I 期临床试验。
ADC 与癌细胞过度表达的抗原结合，并提供靶向性药物递送，目标是在降低有效载荷脱靶毒性的同时提高细胞毒素的治疗效果。通过适当的抗原选择和足够、可测量的抗原阈值靶点，这些新药物可能为克服卵巢癌对标准化疗的耐药性提供一种更好的策略。
