Wolf Prize Laureate in Medicine 2015
Affiliation at the time of the award:
Rockefeller University, New York, USA
“for advancing the understanding of the molecular basis of the immune response”.
Jeffery Ravetch (Born in 1951) revealed the essential mechanisms by which antibodies mediate and regulate their diverse and paradoxical in vivo biological activities. His findings overturned dogma and revealed how antibodies can trigger inflammation, on the one hand, while suppressing inflammatory responses on the other, thereby resolving long-standing observations on the contradictory nature of antibody function. Ravetch’s studies defining how antibodies provide their therapeutic activity through selective engagement of either Fc receptors or SIGN molecules have directed the redesign of antibodies to enhance their therapeutic capacity for treating cancer and inflammatory diseases. As a direct result of his work, over a dozen therapeutic antibodies selectively engineered for either activation or inhibitory Fc receptor binding have been introduced into clinical trials, advancing toward approval. Ravetch’s demonstration of the dominance of the Fc receptor pathway in the mechanism by which pathological immune complexes trigger inflammation has led to the development and clinical testing of small molecule inhibitors of these signaling pathways for the treatment of autoimmune disorders.
Jeffrey Ravetch, John Kappler, and Philippa Marrack are awarded the Wolf Prize for making major contributions to the understanding of the key antigen-specific molecules, the T cell receptor for antigen and antibodies, and how these molecules participate in immune recognition and effector function. Working together, Drs Kappler and Marrack were instrumental in documenting that the T cell receptor recognizes antigen differently from B cells, and succeeded in identifying the previously elusive T cell receptor by an ingenious use of monoclonal T cells and monoclonal antibodies.
Jeffrey Ravetch has studied the heterogeneous effector function of antibody molecules and has documented the importance of diverse receptors for the constant “Fc” part of antibody molecules. He cloned many of these receptors for the immunoglobulin Fc region and showed their importance in mediating antibody function in normal and pathological states. Together, Ravetch, Kappler , and Marrack, have contributed much to the understanding of the molecular basis of the immune response in health and disease.