PD-L1 Antibodies ‘Highly Concordant’

Variability in the assessment of programmed cell death ligand 1 expression is likely not attributable to the antibody used

medwireNews: Discordance between companion diagnostic tests measuring the expression level of programmed cell death ligand 1 (PD-L1) is not due to the antibody, say researchers who found that most PD-L1 antibodies used currently have a comparable ability to bind the protein.

They explain that PD-L1 expression is used to identify responders and guide treatment with programmed cell death 1 (PD-1) inhibitors in clinical trials. But substantial differences in classifying tumour samples have been seen with two validated PD-L1 antibodies, which could be due to tissue heterogeneity or inconsistency among the antibodies.

To analyse antibody variability, the team used tumour samples with a range of PD-L1 expression from 30 non-small-cell lung cancer patients as well as normal tissue and cell line controls to develop an index tissue microarray. PD-L1 expression on the array was evaluated by quantitative immunofluorescence (QIF) and chromogenic immunohistochemistry (IHC) using six different PD-L1 monoclonal antibodies.

Of the four antibodies for which QIF was successfully performed, E1L3N had the lowest concordance relative to the others when assessing PD-L1 expression in tumour samples – specifically, the correlation coefficient was 0.42, 0.58 and 0.68 compared with SP263, SP142 and 9A11, respectively.

The concordance improved, however, for the cell line samples, with corresponding values of 0.83, 0.86 and 0.90. And this was validated using a commercially available 15-spot cell line microarray that expresses a range of controlled levels of PD-L1 (negative, low, medium and high protein-expressing cell lines). Correlation coefficients for the tested antibodies ranged from 0.89 to 0.94.

The 15-spot microarray was also used to test the concordance of all six antibodies (28-8 and 22c3 in addition to the four above) in measuring PD-L1 expression by chromogenic IHC. Once again, the antibodies were “highly concordant”, with correlation coefficients ranging from 0.76 to 0.99, the team reports in JAMA Oncology.

Therefore, our results 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”, conclude David Rimm, from Yale University School of Medicine in New Haven, Connecticut, USA, and co-workers.

 

References

Gaule P, Smithy JW, Toki M, et al. A quantitative comparison of antibodies to programmed cell death 1 ligand 1. JAMA Oncol; Advance online publication 18 August 2016

doi: 10.1001/jamaoncol.2016.3015

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