Validation of Immunomonitoring Methods for Application in Clinical Studies: The HLA-Peptide Multimer Staining Assay

Cytometry B Clin Cytom. 2018 Mar;94(2):342-353. doi: 10.1002/cyto.b.21397. Epub 2016 Jul 22.

Abstract

Background: Validated assays are essential to generate data with defined specificity, consistency, and reliability. Although the process of validation is required for applying immunoassays in the context of clinical studies, reports on systematic validation of in vitro T cell assays are scarce so far. We recently validated our HLA-peptide multimer staining assay in a systematic manner so as to qualify the method for monitoring antigen-specific T cell responses after immunotherapy.

Methods: Parameters of the assay, specificity, precision, linearity, sensitivity, and robustness were assessed systematically. Experiments were designed to address specifically each parameter and are detailed.

Results: Nonspecific multimer staining was below the acceptance limit of 0.02% multimer(+) CD8(+) cells. The assay showed acceptable precision in all dimensions it was repeated (CV < 10%) and also demonstrated a linear detection (R2 > 0.99) of antigen specific cells.

Conclusions: We succeeded in validating the HLA-multimer staining assay in a systematic manner. Additionally, we propose a technical framework and recommendations that can be applied for validating other T cell assessment methods. © 2016 International Clinical Cytometry Society.

Keywords: HLA-multimer; assay validation; biomarker; immunotherapy; mmunomonitoring.

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology
  • HLA Antigens / immunology*
  • Humans
  • Immunoassay / methods
  • Immunotherapy / methods
  • Peptides / immunology*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Staining and Labeling / methods

Substances

  • HLA Antigens
  • Peptides