CBE Seminar - Blaise Kimmel
130 CBEC
151 W Woodruff Ave
Columbus, OH 43210
United States
Engineering Protein Scaffolds as Programmable Immunotherapies
Blaise Kimmel, Postdoctoral Research Fellow, Department of Chemical and Biomolecular Engineering, Vanderbilt University
Abstract
Advances in synthetic biology have led to on-demand antibody therapies that can significantly improve treatment outcomes for patients by targeting tumors discriminately, leaving healthy cells unaffected. However, our inability to program the structure of these therapeutics continues to hamper their optimization for efficacy and contributes to off-target immunogenic responses, an inability to penetrate solid-tumors, and high dosage requirements. My research focuses on developing the next-generation of a protein assembly method that can address these limitations, known as the ‘megamolecule’ strategy. Megamolecules offer advantages of precise, programmable control over the specificity, orientation, and stoichiometry of antibody domains within a nanostructure, which can be tailored for the synthesis of high-impact and clinically important immunotherapies. In this talk, I will first discuss three engineering principles – modularity, functionality, scalability – that are critical to the design, synthesis, and utility of point-of-care protein therapeutics. My findings focus on the design and integration of an orthogonal enzyme-inhibitor chemistry to expand the tunability of megamolecule function, through structural changes, and demonstrate an enhancement in their potential as world-class cancer therapeutics. I will next discuss the construction of rationally designed, logic-gated immunotherapies to tune differential release of an active immunotherapy agent for optimization of CD8+ T cell priming and infiltration over time. This approach will advance the field of immunoengineering by performing a critical investigation into the chemical design elements and mechanisms of action necessary to yield precise control over the spatial delivery and temporal activation of immunostimulatory agents, studies that will lay a strong foundation for future clinical validation of this therapeutic strategy.
Bio
Blaise Kimmel is a Postdoctoral Research Fellow in the Department of Chemical and Biomolecular Engineering at Vanderbilt University. Dr. Kimmel earned degrees in Chemical Engineering, including a B.S. at The Ohio State University (Fan Lab), and both an M.S. and Ph.D. at Northwestern University (Mrksich Lab). During his Ph.D., he was a Ryan Fellow in Nanotechnology, a Northwestern Graduate Teaching Fellow, and a recipient of the NSF Graduate Research Fellowship. His current work is focused on developing point-of-care immunotherapies and medicines through the integration of ideas from protein synthetic biology, synthetic organic chemistry, and T-cell immunology.