Farolfi Alberto, Schepisi Giuseppe, Conteduca Vincenza, Burgio Salvatore Luca, Lolli Cristian, De Giorgi Ugo
a Department of Medical Oncology , Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS , Meldola , Italy.
Expert Opin Drug Metab Toxicol. 2016 Sep;12(9):1089-96. doi: 10.1080/17425255.2016.1214713. Epub 2016 Jul 29.
Nivolumab is a recombinant, humanized monoclonal antibody that binds PD-1. The binding of PD-1 with PD-L1, expressed on antigen-presenting cells and tumor cells, suppresses the ability of T-lymphocytes to recognize and destroy tumor cells. Nivolumab reverts this inhibitory signal and has led to a significant prolongation of overall survival in patients with metastatic renal cell carcinoma (RCC).
The rationale for immunotherapy in metastatic RCC, key immune checkpoint pathways, nivolumab pharmacodynamics, results from the main clinical trials, and predictors of response are discussed.
Nivolumab demonstrated a statistically significant advantage over everolimus in overall survival in metastatic RCC patients after first-line antiangiogenic therapy. Nevertheless, a number of issues remain to be resolved regarding the use of this drug in RCC. It is now imperative to identify which patients can benefit most from immunotherapy and studies are ongoing to define its role in other settings and/or in combinations with antiCTLA4 or antiangiogenic drugs.
纳武单抗是一种重组人源化单克隆抗体，可与程序性死亡受体1（PD-1）结合。抗原呈递细胞和肿瘤细胞上表达的PD-1与程序性死亡配体1（PD-L1）结合，会抑制T淋巴细胞识别和摧毁肿瘤细胞的能力。纳武单抗可逆转这种抑制信号，并显著延长转移性肾细胞癌（RCC）患者的总生存期。
本文讨论了转移性RCC免疫治疗的基本原理、关键免疫检查点途径、纳武单抗的药效学、主要临床试验结果以及反应预测因素。
在一线抗血管生成治疗后的转移性RCC患者中，纳武单抗在总生存期方面显示出优于依维莫司的统计学显著优势。然而，在RCC中使用这种药物仍有许多问题有待解决。现在迫切需要确定哪些患者能从免疫治疗中获益最多，并且正在进行相关研究以明确其在其他情况下和/或与抗细胞毒性T淋巴细胞相关抗原4（antiCTLA4）或抗血管生成药物联合使用时的作用。
