Design and analysis of immune-evading enzymes for ADEPT therapy

Abstract

The unparalleled specificity and activity of therapeutic pro-teins has reshaped many aspects of modern clinical prac-tice, and aggressive development of new protein drugs promises a continued revolution in disease therapy. As a result of their biological origins, however, therapeutic pro-teins present unique design challenges for the biomolecular engineer. For example, protein drugs are subject to immune surveillance within the patient’s body; this anti-drug immune response can compromise therapeutic effi-cacy and even threaten patient safety. Thus, there is a growing demand for broadly applicable protein deimmuni-zation strategies. We have recently developed optimization algorithms that integrate computational prediction of T-cell epitopes and bioinformatics-based assessment of the struc-tural and functional consequences of epitope-deleting muta