Combining multiple binding domains into single macromolecular assemblies enables novel approaches to cancer therapeutic development. Examples of such multispecific strategies will be presented, including: pretargeted radioimmunotherapy; triepitopic receptor clustering and downregulation; and targeted endosomal potentiation for macromolecular payload release. The primary synthetic approach is to use combinatorial libraries of protein displayed on the surface of yeast cells, and to select the desired binding properties by directed evolution. A common analytical thread throughout this work is to formulate simple, reductionist kinetic schema for these complex systems that help to elucidate key parameters and rate processes.
Professor K. Dane Wittrup is the Carbon P. Dubbs Professor of Chemical Engineering and Biological Engineering at the Massachusetts Institute of Technology, and the Associate Director of the Koch Institute for Integrative Cancer Research. From 1989-1999 he was Assistant Professor, Associate Professor, and then J. W. Westwater Professor of Chemical Engineering, Bioengineering, and Biophysics at the University of Illinois in Champaign/Urbana.
Prof. Wittrup received a B.S. in Chemical Engineering Summa cum Laude in 1984 from the University of New Mexico, and a Ph.D. in Chemical Engineering from the California Institute of Technology in 1988 under the thesis direction of Prof. James Bailey. Following a year of postdoctoral research at Amgen (Thousand Oaks, CA), Dr. Wittrup joined the faculty at the University of Illinois.
Wittrup’s research program is focused on protein engineering of biopharmaceutical proteins by directed evolution. Areas of interest include: pretargeted radioimmunotherapy; biological response modification of EGFR; and immunotherapy of cancer via engineered cytokines and vaccines.
Prof. Wittrup has received the following awards and honors recognizing his scholarship: the A. McLaren White Award, for First Prize in the National American Institute of Chemical Engineers Student Design Contest (1984); the Presidential Young Investigator Award of the National Science Foundation (1990-1995); the Allan P. Colburn Award of the American Institute of Chemical Engineers, for excellence in publications for an individual under the age of 35 (1998); the University of New Mexico College of Engineering Distinguished Young Alumnus Award (2000); the Dow Chemical Company Teaching Award(1989); the UIUC School of Chemical Sciences Award for Excellence in Teaching (1993); the UIUC College of Engineering Anderson Award for Undergraduate Advising (1991, 1994); the J.R. Mares Professorship (1999-2007); the C.P. Dubbs Professorship (2007-); induction as a Fellow of the American Institute of Medical and Biological Engineers (1999); induction as Fellow, American Association for the Advancement of Science (2011); and Member, National Academy of Engineering (2012).