Antibody–drug conjugates (ADCs) consist of an antibody backbone that recognizes and binds to a target antigen expressed on tumor cells and a small molecule chemotherapy payload that is conjugated to the antibody via a linker. ADCs are one of the most promising therapeutic modalities for the treatment of various cancers. However, many patients have developed resistance to this form of therapy. Extensive efforts have been dedicated to identifying an effective combination of ADCs with other types of anticancer therapies to potentially overcome this resistance. A recent clinical study demonstrated that a combination of the ADC enfortumab vedotin (EV) with the immune checkpoint inhibitor (ICI) pembrolizumab can achieve remarkable clinical efficacy as the first-line therapy for the treatment of locally advanced or metastatic urothelial carcinoma (la/mUC)—leading to the first approval of a combination therapy of an ADC with an ICI for the treatment of cancer patients. In this review, we highlight knowledge and understanding gained from the successful development of EV and the combination therapy of EV with ICI for the treatment of la/mUC. Using urothelial carcinoma as an example, we will focus on dissecting the underlying mechanisms necessary for the development of this type of combination therapy for a variety of cancers.
抗体药物偶联物（ADC）由识别并结合肿瘤细胞表面靶抗原的抗体骨架，以及通过连接子与抗体偶联的小分子化疗载荷组成。ADC是治疗多种癌症最具前景的治疗策略之一。然而，许多患者已对该疗法产生耐药性。目前研究正致力于探索ADC与其他抗癌疗法的有效联合方案，以期克服耐药问题。近期一项临床研究表明，ADC药物enfortumab vedotin（EV）与免疫检查点抑制剂（ICI）帕博利珠单抗的联合方案，作为局部晚期或转移性尿路上皮癌（la/mUC）的一线治疗显示出卓越的临床疗效——这标志着ADC与ICI联合疗法首次获批用于癌症患者的治疗。本综述重点阐述从EV成功研发及其与ICI联合治疗la/mUC方案中获得的认知与理解。以尿路上皮癌为例，我们将深入剖析开发此类联合疗法治疗多种癌症所需的内在机制。
肿瘤(癌症)患者之家