A Quantitative Comparison of Antibodies to Programmed Cell Death 1 Ligand 1.
A Quantitative Comparison of Antibodies to Programmed Cell Death 1 Ligand 1.
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DOI：
10.1001/jamaoncol.2016.3015
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发表时间：
2017-02-01
期刊：
影响因子：
28.4
通讯作者：
Rimm DL
中科院分区：
文献类型：
--
作者：
Gaule P;Smithy JW;Toki M;Rehman J;Patell-Socha F;Cougot D;Collin P;Morrill P;Neumeister V;Rimm DL
在与FDA相互作用的不同阶段，至少有四种PD-L1免疫组织化学测定法作为伴随或补充诊断检测，以从PD-1轴治疗中获益。已发表了每种检测试剂盒用于选择对治疗有反应的患者的性能，但尚未发表将这些检测试剂盒相互比较或与PD-L1直接测量进行比较的数据。为了确定抗体试剂是否可互换，我们使用六种单克隆抗体（SP142、E1 L3 N、9A 11、SP263、22 c3和28-8）定量比较了PD-L1蛋白的表达。为了测试蛋白质测量，而不是临床实用性，我们创建了一个PD-L1指数组织微阵列，包括细胞系和组织对照，以及30个具有PD-L1表达全动态范围的NSCLC病例。然后，我们使用一系列受控蛋白表达细胞系，在市售的、遗传上确定的PD-L1工程化细胞系阵列上验证了我们的结果。通过定量免疫荧光和定量显色评估来测量蛋白水平。在PD-L1索引组织微阵列中，4种抗体之间的一致性显示，通过QIF，肿瘤组织核心的回归（R2值）在0.42-0.91之间，细胞系核心的回归（R2值）在0.83-0.97之间。当在等基因细胞系中使用显色染色时，所有六种抗体均显示出高水平的一致性（R2范围为0.76至0.99）。由于抗体高度一致，因此这些结果表明基于使用这些抗体的测定可产生一致的结果。他们进一步表明，先前描述的组织中PD-L1表达的差异与所用抗体无关，可能是由于肿瘤异质性、检测/平台特异性变量或其他因素所致。
There are at least four immunohistochemistry assays for PD-L1 at various stages of interaction with the FDA as companion or complementary diagnostic tests for benefit from PD-1 axis therapies. The performance of each assay for selection of patients that respond to therapy has been published, but no data has been published that compares the assays to one another or to direct measurements of PD-L1. To determine whether the antibody reagents are interchangeable, we quantitatively compared expression of PD-L1 protein using six monoclonal antibodies (SP142, E1L3N, 9A11, SP263, 22c3 and 28-8). To test for protein measurement, rather than clinical utility, we created a PD-L1 index tissue microarray including cell line and tissue controls, in addition to 30 NSCLC cases with full dynamic range of PD-L1 expression. We then validated our results on a commercially available, genetically defined PD-L1 engineered cell line array with a range of controlled protein expressing cell lines. Protein levels were measured by both quantitative immunofluorescence and quantitative chromogenic assessment. Concordance between 4 antibodies showed regression (R2 values) between 0.42-0.91 for tumor tissue cores and 0.83-0.97 for cells line cores by QIF in the PD-L1 index tissue microarray. All six antibodies showed high levels of concordance (R2 ranging from 0.76 to 0.99) when using chromogenic staining in isogenic cell lines. Since the antibodies are highly concordant, these results suggest that assays based on the use of these antibodies could yield concordant results. They further suggest that previously described differences in PD-L1 expression in tissue is independent of the antibody utilized and likely due to tumor heterogeneity, assay/platform-specific variables or other factors.