Protein engineering affords researchers the unprecedented capacity to create new molecules with novel and therapeutically useful activities. Researchers have traditionally taken an unbiased approach to protein engineering, but as our knowledge of protein structure-function relationships advances, we have the exciting opportunity to apply molecular principles to guide engineering. Leveraging cutting-edge tools and exclusive expertise in structural biology and molecular design, the Spangler Lab implements a unique structure-based engineering approach to elucidate the determinants of protein activity and inform drug development.
We are particularly interested in engineering antibodies to bias immune activity for applications in immunological disorders such as cancer and diabetes. For over 20 years, antibodies have served as the most powerful tool in immunotherapy, acting through a range of mechanisms including target protein inhibition, immune cell recruitment, delivery of cytotoxic moieties, and modulation of host response. However, antibody efficacy is hampered by acquired resistance and target mutation, necessitating the development of new molecules that act through complementary mechanisms. Building on biophysical insights and new engineering platforms developed in our group, we discover, deliver, and preclinically evaluate antibodies that recruit novel mechanisms to target immune diseases.
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