Use of Ella® to facilitate drug quantification and antidrug antibody detection in preclinical studies.

Aim: To explore the usability of the Ella® platform for preclinical analysis of therapeutic antibodies and antidrug antibodies (ADA). Experimental: Two well-established ELISAs for the measurement of human IgG and ADA were transferred to the Ella platform. ELISA and the Ella platform were compared using assay qualification data and results of preclinical sample analysis. Results: The performance and results of both assays on the Ella platform were comparable to those of ELISA. The Ella platform had several advantages, including time efficiency, low sample consumption and a high degree of automation. ADA were assessed on Ella for the first time. Conclusion: The Ella platform is a promising tool for the analysis of preclinical samples.

Generic anti-drug antibody assay with drug tolerance in serum samples from mice exposed to human antibodies.

Knowledge of the anti-drug antibody (ADA) status is necessary in early research studies. Because specific assay materials are sparse and time is pressing, a generic assay format with drug tolerance for detection of ADAs in serum samples from mice exposed to immunoglobulin G (IgG) or antigen-binding fragments (Fabs) is highly desirable. This article describes a generic immune complex assay in the sandwich enzyme-linked immunosorbent assay (ELISA) format based on (i) transformation of free ADAs to immune complexes by preincubation with excess drug, (ii) the use of a murine anti-human Fab constant domain Fab as capture reagent, (iii) detection of the immune complexes by a peroxidase-labeled rabbit anti-murine Fc antibody, and (iv) ADA-positive control conjugates consisting of human Fab and murine IgG. Results of the experiments suggest that the generic immune complex assay for mouse serum samples was at least equivalent to specific ADA immune assays and even superior regarding drug tolerance. The generic immune complex assay confers versatility as it detects ADAs in complex with full-length IgG as well as with Fabs independent of the target specificity in mouse serum samples. These features help to save the sparse amounts of specific antibodies available in early research and development and speed up drug candidate selection.