Mitigating target interference challenges in bridging immunogenicity assay to detect anti-tocilizumab antibodies

Bioanalysis. 2024;16(12):587-602. doi: 10.1080/17576180.2024.2349417. Epub 2024 Jul 16.

Abstract

Aim: An assay to detect anti-tocilizumab antibodies in the presence of high levels of circulating target and drug is needed for immunogenicity assessment in comparative clinical studies.Methods: An assay was developed and validated using a combination of blocking agents and dilutions to overcome target interference challenges.Results: No false-positive signal was detected in serum samples spiked with 350-500 ng/ml of IL-6 receptor. As low as 50 ng/ml of positive control antibodies could be detected in the presence of either 500 ng/ml of IL-6 or 250 μg/ml of the drug product. Assay also demonstrated high sensitivity, selectivity and precision.Conclusion: A robust, easy to perform immunogenicity assay was developed and validated for detecting anti-tocilizumab antibodies.

Keywords: anti-drug antibodies; electrochemiluminescence; serum IL-6; serum IL-6 receptor; tocilizumab; validation.

Plain language summary

[Box: see text].

MeSH terms

  • Antibodies / immunology
  • Antibodies, Monoclonal, Humanized* / blood
  • Antibodies, Monoclonal, Humanized* / immunology
  • Humans
  • Immunoassay / methods
  • Interleukin-6 / blood
  • Interleukin-6 / immunology

Substances

  • Antibodies, Monoclonal, Humanized
  • tocilizumab
  • Antibodies
  • Interleukin-6