Challenge: A major problem with protein-based therapeutics is their immunogenicity, i.e. their tendency to trigger an unwanted immune response against themselves. This leads to the activation of immune cells and secretion of anti-drug antibodies (ADA) that may contribute to an inactivation of the biologics and cause adverse clinical events. Therefore, there is a need in the pharmaceutical industry for assays to detect immunogenicity of biologics in a predictive way.

Solution: The team developed a new assay based on the principle of quartz crystal microbalance (QCM), that detects ADA in serum samples from subjects treated with biologics. QCM crystals were modified with a low‐fouling coating known as carboxymethyl‐dextran (CMD) which reduces non‐specific binding of proteins and cells. Such crystals specifically detect only ADA and no other serum/blood-borne cells and proteins. Furthermore, the team has developed an in vitro cell‐based assay that could predict whether a patient could potentially have an immunogenic reaction towards a biologic.

Achievements/Impact: ADA was successfully detected in animal serum and in human sera for patients treated with the biologic Enbrel® (an inhibitor of tumor necrosis factor implicated in inflammatory response). ADA concentrations between 50 ‐ 5000 ng/mL were successfully detected using the QCM instrument. The team has also shown that their in vitro test (based on lymphocyte activation by an antigen presented by dendritic cells) can detect the immune reaction generated by Enbrel®. Both the QCM instrument and the in vitro cell‐based assay is available to the pharmaceutical industry to assess the immunogenicity of biologics.