Recombinant adeno-associated virus (rAAV) vectors are the leading platform for gene delivery in a variety of clinical applications. Patients with pre-existing neutralizing antibodies (NAbs) to AAV are typically excluded from AAV gene therapy trials to ensure transduction efficiency. Anti-AAV NAbs are typically assessed by cell transduction inhibition assays in vitro. However, the inherent variability of a cell-based assay limits the ability to accurately measure the response and presents challenges when used as an enrollment screening test. The ability to minimize the variability and monitor the assay performance over time for long-term use becomes critical for supporting clinical trials. Strategies of using controls flanking the predefined cutoff for assay performance monitoring and bridging different lots of critical reagents, such as AAV reporter due to depletion or expired reagents, without the need to redefine the cutoff will be presented.
Context of Use (COU) concept is not limited to biomarker assays but all types of assays
Upon completion, participant will be able to learn how COU can be applied to immunogenicity assays
Adopt a suitable bioanalytical strategy to monitor assay performance and to guide long-term assay monitoring