Immunosuppression in the era of biological agents

Immunosuppression is the mayor mechanism to prevent allograft rejection and to induce tolerance. Since the first solid organ transplant, the development of safe and effective immunosuppressive regimens was a constant over the last decades. A lot of immunosuppressants have been discovered, and today the immunosuppressive agents are classified in two broad groups: Xenobiotic immunosuppressants and biological immunosuppressants. Xenobiotics, like corticoids and calcineurin and mTOR inhibitors, mainly interfere with the intracellular molecular mechanisms of the various types of cells involved in the immune response and generally these immunosuppressants are used early on in the transplantation process to prevent rejection as well as in long-term maintenance therapy. On the other hand, target molecules of biological immunosuppressants are on the surface of these immunological cells and normally in clinical immunosuppressive protocols have been used as auxiliary agents of xenobiotics to prevent rejection as well as in the treatment of acute rejection. However, these xenobiotics and biological agents have multiple side effects; that is why there has been a search for new drugs to minimise these side effects and to improve patients' quality of life. In this way, new biological agents have been proposed as maintenance immunosuppressive agents. The majority of these new immunosuppressive agents are polyclonal or monoclonal antibodies and recently the so-called fusion proteins may be the start of a new era of biological immunosuppression for maintenance regimens.