Antibodies and antibody-based protein drugs are now widely used in development of biotherapeutics for reasons related to specificity, affinity, immunogenicity and residence time. This talk will describe the application of structure-based computational methods to optimize important antibody properties. Specific attention has been paid to increasing the affinity of antibody-antigen interactions and the results of an effort to improve the affinity of a therapeutic anti-VLA1 antibody will be presented. A crystal structure for a mutant with an order of magnitude affinity improvement shows the predicted interface contacts and yields insights into important aspects of protein-protein interaction design. Vertebrate adaptive immune systems have an accelerated mutation and selection process which provides essential high affinity antibodies. A large-scale sequence analysis of this natural somatic hypermutation process yields complementary insights and engineering strategies.

If you'd like to meet with Dr. Clark during his visit, please contact Prof. Michael Greenfield (greenfield at egr.uri.edu).