Current In Vitro Assays for Prediction of T Cell Mediated Immunogenicity of Biotherapeutics and Manufacturing Impurities

Purpose Biotherapeutics are a large and rapidly growing class of drugs being produced by pharmaceutical companies to treat a diverse range of clinical indications. The overall efficacy and safety of these products can be greatly impacted by their capacity to induce undesired immune responses. This review discusses in vitro cell-based methods used to assess the T cell mediated immunogenicity risk of proteinaceous therapeutic modalities and manufacturing impurities. Methods Here, we outline the potential sources and factors that influence immunogenicity. We present patient and product considerations that should be made in designing appropriate in vitro experiments that evaluate T cell epitopes capable of triggering treatment and outcome impacting anti-drug antibody responses and other adverse events. Results We present the current in vitro assays used to assess T cell activation towards biotherapeutics and the product impurities. Lastly, we outline the caveats, concerns, and challenges that remain with these cell-based assays. Conclusions Data generated from these in vitro antigenicity/immunogenicity assays may be used to derive immunogenicity risk assessments for programs and production processes and provides an opportunity for early selection of candidates or manufacturing impurities with lower likelihood of generating or exacerbating clinical immunogenicity.