Yonsei Med J.  2004 Dec;45(6):991-997. 10.3349/ymj.2004.45.6.991.

FTY720: Mechanism of Action and Potential Benefit in Organ Transplantation

Affiliations
  • 1Novartis Institutes for Biomedical Research, Auto Immunity and Transplantation, WSJ-386.101, CH-4002 Basel, Switzerland. volker.brinkmann@pharma.novartis.com

Abstract

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.

Keyword

FTY720; sphingosine 1-phosphate; sphingosine 1-phosphate receptor agonist; lymphocyte sequestration

MeSH Terms

Animals
Autoimmune Diseases/drug therapy
Clinical Trials
Endothelium, Vascular/drug effects
Humans
Immune System/drug effects
Immunosuppressive Agents/*therapeutic use
*Organ Transplantation
Propylene Glycols/*therapeutic use
Receptors, Lysosphingolipid/agonists
Transplantation Immunology
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