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[抗体药物偶联物作为尿路上皮肿瘤学的新型治疗药物]

[Antibody-drug conjugates as new therapeutic agents in uro-oncology].

作者信息

Grimm Marc-Oliver, Foller Susan, Leeder Mirjam, Leucht Katharina

机构信息

Urologische Klinik und Poliklinik, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland.

出版信息

Urologie. 2023 Jul;62(7):679-684. doi: 10.1007/s00120-023-02118-0. Epub 2023 Jun 9.

Abstract

Antibody-drug conjugates represent a new class of therapeutic agents that are already being used in the field of uro-oncology. They consist of an antibody directed against a specific tumour antigen linked to a cytotoxic substance ("payload") which acts after internalisation into the tumour cell and its release. Currently, approval in the European Union is restricted to enfortumab vedotin which is directed against nectin‑4 and carries the microtubule-inhibiting active ingredient monomethyl auristatin E (MMAE). Enfortumab vedotin is approved for locally advanced or metastatic urothelial carcinoma in the third line of therapy after platinum-based chemotherapy and after therapy with a programmed cell death (ligand) 1 (PD-[L]1) immune checkpoint inhibitor. However, an expansion of the indication of enfortumab vedotin as monotherapy and in combination with PD-(L)1 immune checkpoint inhibitors, as well as approval of other antibody-drug conjugates is expected in the future. This could sustainably change the therapy sequence in urothelial carcinoma. Currently, several clinical trials are recruiting in different therapeutic settings. This article presents the new substance class of antibody-drug conjugates, their mechanism of action, their representatives and clinical studies, and points out practice-relevant side effects and how to deal with them.

摘要

抗体药物偶联物是一类新型治疗药物,已在尿路上皮肿瘤学领域得到应用。它们由针对特定肿瘤抗原的抗体与一种细胞毒性物质(“载荷”)连接而成,该细胞毒性物质在被肿瘤细胞内化并释放后发挥作用。目前,欧盟仅批准了安罗替尼,它靶向nectin-4,并携带微管抑制活性成分单甲基奥瑞他汀E(MMAE)。安罗替尼被批准用于铂类化疗和程序性细胞死亡(配体)1(PD-[L]1)免疫检查点抑制剂治疗后的三线局部晚期或转移性尿路上皮癌。然而,预计未来安罗替尼作为单药治疗以及与PD-(L)1免疫检查点抑制剂联合使用的适应症将会扩大,其他抗体药物偶联物也将获批。这可能会持续改变尿路上皮癌的治疗顺序。目前,有几项临床试验正在不同的治疗环境中招募患者。本文介绍了抗体药物偶联物这一新型物质类别、它们的作用机制、代表药物和临床研究,并指出了与实践相关的副作用以及应对方法。

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