Physico-chemical aspects of formulating next generation biologics, including TCRs (T cell receptors).

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Formulation of protein-based drugs is an important aspect of ensuring stability and efficacy of these drugs when they are delivered to patients. However, fundamental gaps in our knowledge about protein-protein interactions and protein-excipient interactions make this process difficult, since rationalisation of the process is not yet possible. Instead, much formulation is conducted based on prior success with other similar molecules, or indeed product development is abandoned for molecules for which a suitable formulation cannot be found. For many biologics that have been produced for a long time (e.g. insulin and IgGs), prior knowledge exists and formulation for most products is relatively straightforward. However, next generation biologics use different molecule types and new technologies for which existing formulation strategies are not as effective or do not exist. This project will examine one such class of next generation biologics, in the development pipeline at Immunocore. These molecules (TCRs) are sufficiently specific in their biological function, that very low concentrations of molecules are required in the final drug product. Hence, a number of new challenges emerge in how to characterise the molecules and their stability and how to formulate them to reduce protein-surface interactions, which are a more difficult problem in low-concentration formulations. Using a range of different analytical tools and knowhow developed in the Biophysics and Soft matter group at the University of Bristol, we will examine how suitable technologies (spectroscopy, light scattering etc) may be applied in low concentration regimes and examine how specific excipients, such as sugars, amino acids and detergents impact on product stability over time.