High-Sensitivity Immunoassay Platform Evaluation for Pharmacokinetic Analysis of T-Cell Engagers

The development of sensitive and reliable bioanalytical assays for T cell engagers (TCEs) necessitates careful selection of immunoassay platforms capable of measuring extremely low circulating drug concentrations. Traditional ligand binding assay (LBA) platforms, such as electrochemiluminescence (ECL; e.g., MSD) , often lack the sensitivity required to adequately characterize exposure during low dose or priming regimens commonly used with TCEs. In contrast, emerging digital immunoassay technologies—including Simoa® and other single molecule detection platforms—achieve femtomolar sensitivity through molecular isolation and amplified signal generation, enabling quantification well below the detection limits of conventional LBAs. This work compares the performance of three immunoassay platforms—standard MSD, MSD S Plex, and the Quanterix SR X—to evaluate their respective analytical sensitivities as well as operational advantages and limitations. Together, these comparisons provide insight into optimal platform selection for supporting the pharmacokinetic assessment of TCEs across a broad range of anticipated exposure levels.