FTY720: mechanism of action and potential benefit in organ transplantation.
FTY720 is a novel immunomodulator that has proven effective in animal models of transplantation and autoimmunity, has achieved promising results in Phase I and Phase II studies of renal transplantation in humans, and is currently undergoing phase III studies. FTY720 acts as a high-affinity agonist at the sphingosine 1-phosphate receptor-1 (S1P1), where it internalises the receptor and causes alterations to the normal circulation of lymphocytes between the blood and lymphoid tissue. Unlike conventional immunosuppressants, FTY720 does not impair the activation, proliferation or effector functions of T- and B-cells. Further development of FTY720 is in progress, including trials in autoimmune disorders as well as transplantation. This review summarises the mechanism of action of FTY720, its effects in models of transplantation and autoimmunity, and results from clinical trials in humans.
Brinkmann
Volker
V
Novartis Institutes for Biomedical Research, Auto Immunity and Transplantation, WSJ-386.101, CH-4002 Basel, Switzerland. volker.brinkmann@pharma.novartis.com
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy; D002986:Clinical Trials as Topic; D004730:Endothelium, Vascular / Q000187:drug effects; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007107:Immune System / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016377:Organ Transplantation; D011409:Propylene Glycols / Q000627:therapeutic use*; D049349:Receptors, Lysosphingolipid / Q000819:agonists; D013110:Sphingosine / Q000031:analogs & derivatives; D014181:Transplantation Immunology
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine