title: Development of an automated PD-L1 immunohistochemistry (IHC) assay for non-small cell lung cancer.
abstract: 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.
authors: *Dako North America Inc., Carpinteria ‡Keck School of Medicine of the University of Southern California, Los Angeles, CA †Bristol-Myers Squibb Inc., Princeton, NJ.
authors: Therese
authors: T
authors: Phillips
authors: Pauline
authors: P
authors: Simmons
authors: Hector D
authors: HD
authors: Inzunza
authors: John
authors: J
authors: Cogswell
authors: James
authors: J
authors: Novotny
authors: Clive
authors: C
authors: Taylor
authors: Xiaoling
authors: X
authors: Zhang
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D001331:Automation; D060890:B7-H1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; C423236:CD274 protein, human