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阿替利珠单抗:一种用于癌症治疗的新型程序性死亡配体1(PD-L1)抑制剂,重点用于膀胱癌和非小细胞肺癌。

Atezolizumab: A novel PD-L1 inhibitor in cancer therapy with a focus in bladder and non-small cell lung cancers.

作者信息

Krishnamurthy A, Jimeno A

机构信息

Department of Medicine, Division of Medical Oncology and Developmental Therapeutics Program, University of Colorado Cancer Center, Aurora, Colorado, USA.

出版信息

Drugs Today (Barc). 2017 Apr;53(4):217-237. doi: 10.1358/dot.2017.53.4.2589163.

Abstract

In recent years, immunotherapy has come to the forefront as a major development in cancer treatment. Evasion of the immune system by tumor cells has been identified as one of the hallmarks of cancer and multiple therapies have been developed to counter this process. Programmed cell death 1 ligand 1 (PD-L1), a ligand to programmed cell death protein 1 (PD-1), is expressed by many cancer cells and the binding of PD-L1 to PD-1 results in the suppression of T-cell-mediated immune response against cancer cells. Atezolizumab is a monoclonal antibody that binds to PD-L1 and blocks its interaction with PD-1, thereby enhancing T-cell activity against tumor cells. Atezolizumab has been shown to be well tolerated with no dose-limiting toxicities in phase I trials. Atezolizumab was approved by the U.S. Food and Drug Administration in 2016 for the treatment of platinum-resistant metastatic non-small cell lung cancer (NSCLC) and urothelial cancer based on phase II and preliminary phase III studies that have shown significant improvement in objective response rate and median overall survival. There are 117 ongoing clinical trials of atezolizumab currently. Given its efficacy in NSCLC and urothelial carcinoma, atezolizumab holds much potential in the future of cancer therapeutics.

摘要

近年来,免疫疗法已成为癌症治疗领域的一项重大进展,处于前沿地位。肿瘤细胞对免疫系统的逃避已被确认为癌症的标志之一,并且已经开发出多种疗法来对抗这一过程。程序性细胞死亡蛋白1配体1(PD-L1)是程序性细胞死亡蛋白1(PD-1)的配体,许多癌细胞都会表达它,PD-L1与PD-1的结合会导致针对癌细胞的T细胞介导的免疫反应受到抑制。阿替利珠单抗是一种单克隆抗体,它与PD-L1结合并阻断其与PD-1的相互作用,从而增强T细胞对肿瘤细胞的活性。在I期试验中,阿替利珠单抗已显示出良好的耐受性,没有剂量限制性毒性。基于II期和初步III期研究显示客观缓解率和中位总生存期有显著改善,阿替利珠单抗于2016年被美国食品药品监督管理局批准用于治疗铂类耐药转移性非小细胞肺癌(NSCLC)和尿路上皮癌。目前有117项正在进行的阿替利珠单抗临床试验。鉴于其在NSCLC和尿路上皮癌中的疗效,阿替利珠单抗在未来癌症治疗中具有很大潜力。

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