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Brief Report
February 2017

A Quantitative Comparison of Antibodies to Programmed Cell Death 1 Ligand 1

Author Affiliations
  • 1Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
  • 2Horizon Discovery PLC, Cambridge, United Kingdom
JAMA Oncol. 2017;3(2):256-259. doi:10.1001/jamaoncol.2016.3015
Key Points

Question  Do the 4 drug-matched companion diagnostic antibodies for PD-1 axis therapies all produce the same results?

Findings  In this study, 3 key components of diagnostic tests were assessed: the primary antibody, assay-specific variables related to the staining platform, and immunohistochemical assessment of tissue. All antibodies tested were concordant.

Meaning  Discordance of the companion diagnostic test is not attributable to the antibody but rather to inherent tumor heterogeneity or assay- or platform-specific variables.

Abstract

Importance  Assessment of PD-L1 (programmed cell death 1 ligand 1) expression by immunohistochemical analysis has been used as a predictive diagnostic test to identify responders and guide treatment in trials of the PD-1 (programmed cell death 1) axis inhibitors. The definition of PD-L1 positive lacks standardization, and prediction of response by immunohistochemical analysis is additionally limited by the subjective nature of this technique.

Objective  To examine whether PD-L1 antibody reagents are interchangeable by quantitatively comparing the expression of the PD-L1 protein.

Design, Setting, and Participants  In this immunohistochemistry standardization study, 30 randomly selected cases of lung cancer resected from January 1, 2008, through December 31, 2009, were obtained from Yale Pathology Archives with a range of expression of PD-L1. To test for protein measurement, rather than clinical utility, a PD-L1 index tissue microarray, including cell line and tissue controls, was used. The results were then validated on a commercially available, genetically defined PD-L1 engineered cell line array with a range of controlled protein-expressing cell lines using 6 monoclonal antibodies (SP142, E1L3N, 9A11, SP263, 22c3, and 28-8). Protein levels were measured by quantitative immunofluorescence and quantitative chromogenic assessment. Data analysis was performed from September 2015 through May 2016.

Results  Concordance between 4 antibodies revealed regression for tumor tissue cores (R2 = 0.42-0.91) and cell line cores (R2 = 0.83-0.97) by quantitative immunofluorescence in the PD-L1 index tissue microarray. All 6 antibodies had high levels of concordance (R2 = 0.76-0.99) when using chromogenic staining in isogenic cell lines.

Conclusions and Relevance  Because 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 are independent of the antibody used and likely attributable to tumor heterogeneity, assay- or platform-specific variables, or other factors.

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