Sensitivity and drug tolerance of antidrug antibody assays in relation to positive control characteristics.

AIM

Detection and characterization of antidrug antibodies (ADA) play a key role in understanding the relation of ADA with safety and efficacy. Positive controls (PCs) are used to estimate the sensitivity and assay sensitivity in the presence of drug (drug tolerance) of assays to detect ADA. We investigated a number of factors that may drive sensitivity and drug tolerance.

RESULTS

We found no correlation between affinity and sensitivity and sensitivity in the presence of drug in multiple assays with two antibody-drug conjugates. Multiple factors that influenced sensitivity and drug tolerance were observed, yet these had limited overall predictive value for all investigated assay formats, PCs and compounds.

CONCLUSION

Assay sensitivity and drug tolerance as studied here, are likely driven by multiple factors such as cut point confidence level, stoichiometry of PC-drug complexes and presentation of epitopes.