Immunosuppression: ongoing clinical trials

Monoclonal antibodies: Monoclonal antibodies have been humanized to improve their duration of action and their tolerance. Lymphocyte-depleting humaniz ed anti-CD3 antibodies are globally well tolerated. Coupled with an immunot oxin, Campath 1H, a humanized anti-CD3 antibody with specific anti-CD52 dep leting properties which also depletes immunocompetent cells, is being teste d. There is increasing interest in the use of monocolonal antibodies in com bination with rapamycin. Sirolimus and everolimus: The half-life of sirolimus is twice that of evero limus. Otherwise quite similar, these compounds have dose-dependent side ef fects: leukopenia, thrombocytopenia, hyperlipidemia. There use allows a low er dosage for the calcineurin inhibitor. Sirolimus is particularly active i n reducing intimal proliferation within the vessel walls. Precise indicatio ns at the present time include induction of tolerance, withdrawal of the ca lcineurin inhibitor, use of low-dose calcineurin inhibitor, and corticoster oid withdrawal. Eliminating the side effects of corticosteroids: Complications resulting fr om the use of corticosteroids, particularly bone complications, are still a problem with the low doses used in long-term regimens for transplant recip ients. Several means have been proposed to reduce the risk Total withdrawal is possible, but the risk of an increased rate of acute rejection limits i ndications. It appears that total withdrawal then complete abstention is no t compatible immunologically, Immunosuppressors in perspective: Three groups of compounds have immunosupp ressor potential: anti-adhesion molecule antibodies, costimulation blockers , and molecules inhibiting T-lymphocyte activators and their signalization factors.