Immunogenicity Testing by Electrochemiluminescent Detection for Antibodies Directed against Therapeutic Human Monoclonal Antibodies

Abstract

Monitoring the immune response against human therapeutic monoclonal antibodies is an important component of preclinical and clinical trials to assess drug exposure, efficacy, and safety (1)(2). Detection of antibodies (analyte) directed against therapeutic antibodies (drug) is difficult because of the similarity of structure between drug and analyte and the high concentrations of drug present in serum, particularly during preclinical toxicology studies (3)(4). The purpose of this study was to develop a robust assay format applicable across species and drug compounds for rapid method development and validation. We developed 5 assays to detect antibodies against 5 distinct monoclonal antibody therapeutic drug products. Detection was dependent on bivalent antibodies binding both biotin- and ruthenium-conjugated drug compounds (for a schematic of the assay, see Fig. 1 of the Data Supplement that accompanies the online version of this abstract at http://www.clinchem.org/content/vol51/issue10/). This “bridging” assay format eliminated the need for species–specific secondary antibodies and provided assay consistency in different serum matrices as a drug product moves from preclinical to clinical development. …