a Division of Medical Oncology , Instituto do Câncer do Estado de São Paulo, Hospital Sírio Libanês , São Paulo , Brazil.
b Thoracic Oncology Service, Department of Medicine , Memorial Sloan Kettering Cancer Center , New York , NY , USA.
Expert Rev Clin Pharmacol. 2017 Sep;10(9):935-945. doi: 10.1080/17512433.2017.1356717. Epub 2017 Jul 27.
The immune system can restrain or promote cancer development and growth. Antibodies targeting immune checkpoints have revolutionized cancer treatment. Among the best responses have been in non-small cell lung cancer (NSCLC) which is largely caused by chronic exposure to carcinogens; associated with high neoantigen creation and sensitization to immune recognition. Atezolizumab was the first approved antibody that targets the PD-1 ligand (PD-L1). Areas covered: This drug profile article covers the basics of the cancer-immunity cycle and reviews some aspects of innate and adaptive immunology. We discuss the discovery of PD-L1 and PD-L2 while highlight the potential differences in targeting PD-L1 versus PD-1. In addition, we briefly summarized the available pre-clinical and clinical data of atezolizumab use in NSCLC. A special section covers the challenges of PD-L1 immunohistochemistry assay. Expert commentary: PD-1:PD-L1 blockade has taken the lead in the immunotherapeutics field and represents the backbone of developing combination immunotherapies. Atezolizumab represents a step forward in the treatment of advanced NSCLC, nonetheless PD1:PD-L1 blockade in early-stage lung cancer is still a matter of debate.
免疫系统可以抑制或促进癌症的发展和生长。针对免疫检查点的抗体已经彻底改变了癌症的治疗方法。在非小细胞肺癌(NSCLC)中,反应最好,因为它主要是由长期接触致癌物质引起的;与高新生抗原的产生和对免疫识别的敏感有关。阿特珠单抗是第一个被批准的针对 PD-1 配体(PD-L1)的抗体。涵盖领域:本文介绍了癌症免疫周期的基础知识,并回顾了先天免疫和适应性免疫的一些方面。我们讨论了 PD-L1 和 PD-L2 的发现,同时强调了靶向 PD-L1 与 PD-1 的潜在差异。此外,我们简要总结了阿特珠单抗在 NSCLC 中的可用临床前和临床数据。特别介绍了 PD-L1 免疫组织化学检测的挑战。专家评论:PD-1:PD-L1 阻断在免疫治疗领域处于领先地位,是开发联合免疫疗法的基础。阿特珠单抗代表了晚期 NSCLC 治疗的一个进步,但 PD1:PD-L1 阻断在早期肺癌中仍然存在争议。