Antibodies (Basel, Switzerland) · 2026
Development and Validation of Cell-Based Bioassay for the Detection of Neutralizing Antibodies to Ocrelizumab in Human Serum Using Antibody-Dependent Cell-Mediated Cytotoxicity Test in a Reporter Cell Line Expressing FcγRIIIa.
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Strizhakova Olga, Poroshin Grigory, Pershin Andrei, Bakhareva Yana, Shevchenko Ivan, Lyagoskin Ivan, Shukurov Rakhim, Khamitov Ravil
Аннотация
BACKGROUND/OBJECTIVES: Ocrelizumab is a humanized monoclonal antibody targeting CD20, approved for the treatment of adult patients with relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS). The neutralizing activity of anti-drug antibodies (ADAs), especially neutralizing ADAs (nADAs) activity, should be examined considering that it can alter pharmacokinetic (PK) and pharmacodynamic (PD) profiles, reduce drug efficacy, and lead to life-threatening adverse events.
METHODS: This article presents data on the development and validation of an assay for neutralizing anti-drug antibodies (nADA) based on ADCC reporter cells for the analysis of patient sera in the context of ocrelizumab clinical studies.
RESULTS: Critical steps and conditions to minimize assay variability were identified. The lower limit of detection was 549.6 ng/mL. The cutoff for nonspecific neutralization was determined as 19.7%. The presence of 0.37-3.0 μg/mL ocrelizumab in a biological sample enables the detection of 1.1-10.0 μg/mL polyclonal anti-ocrelizumab idiotype antibodies, respectively.
CONCLUSIONS: The developed method can be used for immunogenicity studies of medicinal products containing ocrelizumab.
METHODS: This article presents data on the development and validation of an assay for neutralizing anti-drug antibodies (nADA) based on ADCC reporter cells for the analysis of patient sera in the context of ocrelizumab clinical studies.
RESULTS: Critical steps and conditions to minimize assay variability were identified. The lower limit of detection was 549.6 ng/mL. The cutoff for nonspecific neutralization was determined as 19.7%. The presence of 0.37-3.0 μg/mL ocrelizumab in a biological sample enables the detection of 1.1-10.0 μg/mL polyclonal anti-ocrelizumab idiotype antibodies, respectively.
CONCLUSIONS: The developed method can be used for immunogenicity studies of medicinal products containing ocrelizumab.