The assessment of undesirable immunogenicity is a key element in biological drug development. In order to understand any underlying safety concerns, we need to identify if the therapeutic protein triggers unwanted immune responses, as well as the effect and severity these immune reactions have on the biologic’s efficacy and safety.
In a drug development setting, “immunogenicity assay” is often synonymous with “anti-drug antibody (ADA) assay”, as these are the antibodies that may induce unwanted side effects and have been observed in preclinical and clinical studies to cause significant changes in efficacy and safety. Ideally, we aim to see any drug-induced antibody. Therefore, the best method is one that is able to detect ADAs as sensitively and specifically as possible.
This is where the Biacore™ T200 platform comes in. Operated out of our European headquarters in Hamburg, Germany, this platform has the capacity to deliver highly specific analysis, robust data quality, and efficient time-to-results for immunogenicity studies at any phase of development.
How the Biacore™ Platform Works
For immunogenicity studies, Biacore can be used to analyze, characterize, and monitor ADAs and molecular interactions related to kinetics, specificity, and concentration in pre-clinical and clinical assay development. Because it uses SPR, it is able to detect low-affinity ADAs that may mature into higher affinity ADAs over time, and has been shown to detect positive samples much earlier than, for example, immunoassays. This is an important capability because an early detection of immune response may enable us to interfere at an earlier state for the sake of patients’ health and safety.
Additionally, Biacore™ is able to detect ADAs down to nanogram levels. It may not yet by completely clear whether antibodies in the low nanogram range will have clinical significance, but I believe that assays cannot be too overly sensitive, and that seeing all drug-induced antibodies can help guide us to identify clinically meaningful data and more accurately correlate immunogenicity with clinical impact. Biacore™ provides for specific detection and characterization of ADAs of any isotype, which may help determine the clinical relevance of the ADA.
Drug interference is common in immunogenicity assays, when drug present in the sample binds to ADAs and prevents them from binding to the immobilized drug. To mitigate this challenge and the resulting false negatives, Biacore™ automates an acid-dissociation process. Samples are acidified to allow drug-ADA complexes to dissociate, and then neutralized just prior to measurement. Therefore, it enables the detection of ADAs even in the presence of high levels of drug.
A Powerful Platform in the Right Hands
The capabilities of the Biacore™ T200 platform are impressive and have the potential to positively impact immunogenicity studies through highly specific detection and characterization of ADAs. That said, it still requires scientists with the expertise to effectively interpret immunogenicity results and distinguish clinically meaningful data from the rest. Over-interpretation may exclude some patients from beneficial treatment options, and under-interpretation may put patients’ safety at risk. The full value of this innovative platform can only be derived through a deep understanding of the many drug- and disease-specific aspects that impact adverse immune reactions.
To find out how BioAgilytix’s European headquarters combines industry-leading immunogenicity expertise with Biacore’s advanced technology to effectively progress your large molecule study, contact our team today.