Characterization and quantification of therapeutic monoclonal antibodies, anti-drug antibodies and their interactions for clinical applications

Abstract

Therapeutic monoclonal antibodies (mAbs) are experiencing tremendous developments in terms of novel approved products and applications fields. Nonetheless, after administration, mAbs are submitted to a significant number of biological phenomena that may affect their quantity, structure and potency. Moreover, as mAbs are not exempt from adverse effects they can trigger immune responses leading to the expression of anti-drug antibodies (ADAs), potentially impacting their efficacy. This critical review details the different analytical techniques used for the characterization and quantification of mAbs and ADAs in different contexts from routine therapeutic drug monitoring to advanced clinical investigations. In addition, state-of-art approaches providing information regarding mAbs/antigen or mAbs/ADAs interaction such as binding affinities are described through impactful applications. Different analytical approaches are discussed including binding assays like ELISA and chemiluminescent immunoassay. Similarly, molecular interaction analyses are detailed like surface plasmon resonance and mass photometry. Finally, cutting-edge mass spectrometry-based analytical methods are presented with prior liquid chromatography and capillary electrophoresis separation, including the sample purification strategies required for the analysis of biological samples. Thus, the critical review discusses the technical requirements, advantages and limitations of the different analytical techniques in order to position them depending on the context and information required.