Bioanalysis for PK for antibody drug conjugates using ligand binding assay-challenges and bioanalytical strategies.

Abstract

Antibody-drug conjugates (ADCs) represent a rapidly advancing class of biotherapeutics for oncology and immunological indications. Comprehensive pharmacokinetic (PK) characterization is critical for assessing ADCs efficacy, safety, and overall therapeutic performance. Ligand binding assays (LBAs) are widely employed in both academic and industrial settings for the quantitative and semi-quantitative analysis of biologics. These assays rely on specific molecular interactions - commonly between antigens and antibodies or ligands and receptors - and offer high sensitivity, robustness, and cost-efficiency. In ADC bioanalysis, LBAs are utilized to quantify multiple types of analytes, including total antibody and antibody-drug conjugate. However, the development of LBA methods for ADCs is challenged by the structural heterogeneity of these molecules, analyte instability, and the need for high selectivity and sensitivity. This review summarizes the application of LBAs in ADC PK studies, outlines common methodological challenges, and discusses strategic considerations for assay development to ensure accurate and reliable bioanalytical measurements.