Publication / Source: Bioanalysis 11(17)
Authors: Chen J, Garlits J, Dhulipala G et al
Background: Soluble drug target in clinical study samples generated false positive results in anti-drug antibody (ADA) bridging assays due to target-mediated bridging. Results: The combination of two target-blocking reagents and mild basic assay pH resulted in high tolerance to recombinant target protein and reduced levels of positivity in clinical study samples with pharmacokinetic profiles that did not indicate significant ADA response. Testing with low-affinity ADA positive serum from immunized rabbits and known ADA positive samples from nonclinical studies in rats confirmed the assay’s ability to detect ADA positive samples and the minimal impact of basic pH and target-blocking reagents on ADA detection. Conclusion: These strategies provide alternatives for mitigating target interference when standard target-blocking antibodies alone are ineffective.
Biotherapeutics, including fully human therapeutic monoclonal antibodies, have the potential to generate anti-drug antibodies (ADA) that can cause undesired effects, such as loss of drug exposure, loss of efficacy or serious adverse events [1–3]. Therefore, immunogenicity assessment is an important part of the safety testing for all biotherapeutics. Detailed recommendations on immunogenicity testing during various stages of drug development, including those from regulatory agencies [4–9], have been published.