Immunogenicity testing strategy and bioanalytical assays for antibody–drug conjugates

Abstract

Background: Immunogenicity testing is an important component of clinical development for large-molecule biotherapeutics. New complex types of large molecules, such as antibody–drug conjugates (ADCs), require careful evaluation of the testing strategy and bioanalytical assays used to monitor the development of antitherapeutic antibodies. Results: An electrochemiluminescence-based immunoassay for the detection and epitope characterization of anti-ADC antibodies was validated. Using this assay format, antibodies directed against the monoclonal antibody and linker–drug components of the ADC were successfully detected in a multiple-dose rat toxicity study. Conclusion: Immunogenicity assays incorporating epitope determination may provide additional information about the characteristics of induced antitherapeutic antibodies, including the magnitude and timing of the various types of antibody responses.