New therapeutic targets for antibodies and recombinant proteins in organ transplantation

The history of immunosuppression in organ transplantation is an example of evolution from "experimental" medicine/biology to biological knowledge and drug development. For example, in the 1950-60s, azathioprine, a drug first noted for its anti-proliferative/anti-leukemic properties, started to be used as an immunosuppressant after organ transplantation. Cyclosporine A, first considered as an antiprotozoal agent, was subsequently discovered to be a powerful immunosuppressant. In each case, the experimental approach led to the discovery of previously unknown basic molecular mechanisms. Now, the dissection of basic phenomena such as the immunological synapse has generated a large array of new agents (monoclonal antibodies, small molecules, fusion molecules) that may revolutionize the field of organ transplantation by improving patient and allograft survival and by reducing short-and long-term adverse effects. This field also provides examples of direct transfer from basic research to industrial bioengineered immunosuppressants.