Faiena Izak, Cummings Amy L, Crosetti Anna M, Pantuck Allan J, Chamie Karim, Drakaki Alexandra
Department of Urology.
Institute of Urologic Oncology.
Drug Des Devel Ther. 2018 Jan 23;12:209-215. doi: 10.2147/DDDT.S141491. eCollection 2018.
Our expanding knowledge of immunotherapy for solid tumors has led to an explosion of clinical trials aimed at urothelial carcinoma. The primary strategy is centered on unleashing the immune system by releasing the inhibitory signals propagated by programmed cell death-1 (PD-1) and its ligand programmed cell death ligand-1 (PD-L1). Many antibody constructs have been developed to block these interactions and are used in clinical trials. The Food and Drug Administration has already approved a number of checkpoint inhibitors such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibodies including ipilimumab; anti-PD-1 monoclonal antibodies including nivolumab and pembrolizumab; anti-PD-L1 antibodies including atezolizumab, avelumab, and durvalumab. One of the latest inhibitors is durvalumab, which is a high-affinity human immunoglobulin G1 kappa monoclonal antibody and blocks the interaction of PD-L1 with PD-1 and CD80. Currently, there are a number of ongoing trials in advanced urothelial carcinoma both using durvalumab monotherapy and in combination with other targeted therapies. In addition, durvalumab is being investigated in the non-muscle-invasive urothelial carcinoma, which is centered around intravenous formulations. These exciting developments have added a significant number of therapies in a previously limited treatment landscape.
我们对实体瘤免疫疗法的认识不断扩展，引发了针对尿路上皮癌的临床试验热潮。主要策略集中在通过释放程序性细胞死亡蛋白1（PD-1）及其配体程序性细胞死亡配体1（PD-L1）所传播的抑制信号来激活免疫系统。已经开发了许多抗体构建体来阻断这些相互作用，并用于临床试验。美国食品药品监督管理局已经批准了多种检查点抑制剂，如抗细胞毒性T淋巴细胞相关蛋白4（CTLA4）单克隆抗体，包括伊匹木单抗；抗PD-1单克隆抗体，包括纳武单抗和派姆单抗；抗PD-L1抗体，包括阿特珠单抗、阿维鲁单抗和度伐鲁单抗。最新的抑制剂之一是度伐鲁单抗，它是一种高亲和力的人免疫球蛋白G1κ单克隆抗体，可阻断PD-L1与PD-1和CD80的相互作用。目前，有多项针对晚期尿路上皮癌的正在进行的试验，既使用度伐鲁单抗单药治疗，也与其他靶向疗法联合使用。此外，度伐鲁单抗正在非肌肉浸润性尿路上皮癌中进行研究，主要围绕静脉制剂展开。这些令人兴奋的进展在以前有限的治疗领域增加了大量治疗方法。
