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Antibody Drug conjugates: the success of failure

Uwe Gottschalk

As a young scientist, I was interested in antibody–drug conjugates (ADCs) because of my background in immunochemistry and previous experience in the development of antibody derivatives. I was asked to participate in a project involving the conjugation of cytotoxic drugs to monoclonal antibodies that specifically recognized tumor-associated antigens. The idea was based on a concept originally advanced by Paul Ehrlich, to create a magic bullet for cancer treatment, long before such tools became available. Many different toxic substances were available as the payload, most of which had already been used in chemotherapy, albeit with the risk of serious adverse effects due to their nonspecific activity. Chemotherapy needed to be aggressive and oncologists managed a fine line between the quantitative eradication of tumor cells and the serious impact of adverse effects. The study was financed by the European Community under the framework program Europe Against Cancer (1987–2000) and its mission was clear. Little had changed 16 years after the signing of the National Cancer Act (1971), which US President Richard Nixon often referred to as “the war on cancer”, despite dramatic improvements in certain areas of cancer therapy. In the meantime, however, basic research had helped to create a better understanding of cancer biology, improved diagnostics and tumor-associated surface proteins that were thought to be ‘undruggable’ came under scrutiny for targeted therapies.