Fellow

Sir Greg Winter is Head of the Division of Protein & Nucleic Acid Chemistry, MRC. He is a pioneer of protein engineering, using site-directed mutagenesis of the gene to create mutant proteins with novel properties. The greatest medical impact of his work has been in the development of therapeutic antibodies. He developed humanised antibodies by grafting the hypervariable regions from rodent monoclonal antibodies to human antibodies. Such humanised antibodies were mainly of human origin, but had the antigen-binding specificity of the parent rodent antibody. This allowed rodent monoclonal antibodies, potentially immunogenic in humans, to be transformed into therapeutic agents. He was responsible, together with Hermann Waldmann, for the development of the therapeutic antibody Campath-1, used initially to treat non-Hodgkins lymphoma. This was the first reported clinical use of a genetically engineered therapeutic antibody. The technology was licensed widely by the MRC to many companies, and other humanised therapeutic antibodies followed, including. He then developed a revolutionary in vitro approach for making entirely human antigen-specific antibodies including those against human self-antigens. This involved the creation of large combinatorial antibody libraries, and the in vitro selection for antigen binding by phage display. The technology was largely developed at the MRC, and exploited commercially through Cambridge Antibody Technology (CAT) where he acted as the first research Director. This led to the co-development of a human antibody against human TNFalpha between CAT and BASF Pharma. This antibody, Humira, marketed by Abbott for treatment of rheumatoid arthritis, was the first human therapeutic antibody to be approved by the FDA and has had a major impact on disease. At present humanized, human and chimaeric antibodies jostle for use in the clinic. The impact of Winter as scientist, inventor and entrepreneur in rejuvenating what was once “serum therapy” should not be underestimated: of the 14 recombinant therapeutic antibodies currently approved by the FDA, the majority are based on technologies developed by Winter.