Keynote Talk: Thomas Truskett, Professor, University of Texas at Austin
“Structure and dynamics of concentrated monoclonal antibody solutions”
Monoclonal antibodies (mAbs) have become prevalent in treating diseases ranging from COVID-19 to autoimmune disorders and cancer. However, strong mAb-mAb attractions in concentrated solutions can cause reversible oligomers (clusters) to form, leading to increased shear viscosity, and loss of stability. As a result, biopharmaceutical companies invest considerable effort in designing stable, low-viscosity concentrated mAb formulations for processing and subcutaneous injection. Unfortunately, mAb interactions measured under dilute conditions by conventional techniques do not reliably predict behavior at high concentrations. In this talk, we will explore these challenges and potential strategies to address them. Recent work suggests that the strength and geometry of anisotropic mAb-mAb attractions at different pH, salt, and cosolute conditions can be inferred from a combination of small-angle X-ray scattering measurements and coarse-grained molecular simulations. The latter also provides information about cluster-size distributions and mAb coordination numbers, which can be used to understand and predict trends in viscosity and colloidal stability. We will highlight examples of this approach and discuss how it can be integrated with tools from computational chemistry to discover molecular-scale mechanisms.
Biography
Thomas M. Truskett is the Dick Rothwell Endowed Chair in Chemical Engineering and Professor of Chemical Engineering and Physics at the University of Texas at Austin. He earned a bachelor of science in chemical engineering from the University of Texas at Austin in 1996 and a doctoral degree in chemical engineering from Princeton University in 2001, where he studied statistical mechanics of the liquid state, the glass transition, and physics of disordered media. He pursued post-doctoral research at the University of California, San Francisco, where he investigated water, hydrophobic interactions, and modeling of biomolecular systems. In 2002, he joined the faculty of the University of Texas at Austin and served as Department Chair of Chemical Engineering from 2013-2021. Dr. Truskett’s research group explores how interfaces and confinement impact the behavior of soft matter, including molecular fluids, colloidal suspensions, and protein solutions.
