Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey.
Twenty-five years ago, we reported the production of the monoclonal antibody, anti-Tac that identifies the IL-2 receptor alpha subunit and blocks the interaction of IL-2 with this growth factor receptor. In 1997, daclizumab (Zenapax), the humanized form of this antibody, was approved by the FDA for use in the prevention of renal allograft rejection. In addition, we demonstrated that daclizumab is of value in the treatment of patients with noninfectious uveitis, multiple sclerosis, and the neurological disease human T-cell lymphotropic virus I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Others demonstrated therapeutic efficacy with daclizumab in patients with pure red cell aplasia, aplastic anemia, and psoriasis. Thus, translation of basic insights concerning the IL-2/IL-2 receptor system obtained using the monoclonal antibody daclizumab provided a useful strategy for the prevention of organ allograft rejection and the treatment of patients with select autoimmune diseases or T-cell leukemia/lymphoma.
Waldmann
Thomas A
TA
Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH Building 10, Bethesda, Maryland 20892-1374, USA. tawald@helix.nih.gov
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001327:Autoimmune Diseases / Q000188:drug therapy*; D001667:Binding, Competitive / Q000276:immunology; D000077561:Daclizumab; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors / Q000276:immunology; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy; D051379:Mice; D015493:Paraparesis, Tropical Spastic / Q000188:drug therapy; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000276:immunology; D014605:Uveitis / Q000188:drug therapy
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D015375:Receptors, Interleukin-2; D000077561:Daclizumab