Development of an automated PD-L1 immunohistochemistry (IHC) assay for non-small cell lung cancer.
Development of an automated PD-L1 immunohistochemistry (IHC) assay for non-small cell lung cancer.
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DOI：
10.1097/pai.0000000000000256
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Phillips T;Simmons P;Inzunza HD;Cogswell J;Novotny J Jr;Taylor C;Zhang X
文本中提供了补充数字内容。 Nivolumab 是一种全人源 IgG4 程序性死亡 1 (PD-1) 免疫检查点抑制剂抗体，由百时美施贵宝公司开发，在非小细胞肺癌 (NSCLC) 组织学中具有活性，并已获得美国食品和药物管理局批准用于治疗在铂类化疗期间或之后进展的转移性鳞状 NSCLC。 PD-L1 已被研究作为预测临床环境中纳武单抗临床反应的潜在生物标志物。我们报告了一种自动 PD-L1 免疫组织化学 (IHC) 测定，该测定旨在使用 Dako 的 Autostainer Link 48 检测福尔马林固定石蜡包埋的人类肿瘤组织样本中的细胞表面 PD-L1。该测定的一抗是兔单克隆抗人 PD-L1 抗体（克隆 28-8）。 28-8 对 PD-L1 的特异性通过肿瘤细胞系中 PD-L1 的抗原竞争和遗传删除得到证明。在 30 份正常人体组织中进一步评估了 PD-L1 IHC 检测的特异性。 PD-L1 IHC 检测经过优化，可在常规应用中实现高灵敏度和精确度。该测定采用纳武单抗临床研究特有的病理学评分和解释方法。该测定的分析性能经过验证，可用于测定人类 NSCLC 样本中的 PD-L1 状态。该测定和评分方法的临床应用在 3 个临床实验室改进修正案认证的实验室中得到了进一步验证。该检测目前正在各种临床研究中进行研究，以用作体外诊断，以选择和分层接受抗 PD-1 治疗抗体纳武单抗治疗的患者。
Supplemental Digital Content is available in the text. Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune checkpoint inhibitor antibody, developed by Bristol-Myers Squibb Inc., has activity across non–small cell lung cancer (NSCLC) histologies and is Food and Drug Administration approved for treatment of metastatic squamous NSCLC with progression on or after platinum-based chemotherapy. PD-L1 has been investigated as a potential biomarker to predict clinical response to nivolumab in clinical settings. We report an automated PD-L1 immunohistochemistry (IHC) assay, which was developed to detect cell surface PD-L1 in formalin-fixed paraffin-embedded human tumor tissue specimens using Dako’s Autostainer Link 48. The primary antibody for this assay is a rabbit monoclonal anti-human PD-L1 antibody, clone 28-8. The specificity of 28-8 for PD-L1 was demonstrated by antigen competition and genetic deletion of PD-L1 in tumor cell lines. The specificity of the PD-L1 IHC assay was further evaluated in a collection of 30 normal human tissues. The PD-L1 IHC assay was optimized for high sensitivity and precision in routine application. A pathology scoring and interpretation method specific to nivolumab clinical studies was adopted for the assay. The analytical performance of the assay was validated for application in the determination of PD-L1 status in human NSCLC specimens. The clinical application of the assay and scoring method was further validated in 3 Clinical Laboratory Improvement Amendments certified labs. The assay is currently being investigated in a variety of clinical studies for use as an in vitro diagnostic to select and stratify patients for treatment with the anti-PD-1 therapeutic antibody, nivolumab.