Daclizumab (anti-Tac, Zenapax) in the treatment of leukemia/lymphoma.
Daclizumab (Zenapax) identifies the alpha subunit of the interleukin-2 (IL-2) receptor and blocks the interaction of this cytokine with its growth factor receptor. The scientific basis for the choice of the IL-2 receptor alpha subunit as a target for monoclonal antibody-mediated therapy of leukemia/lymphoma is that very few normal cells express IL-2R alpha, whereas the abnormal T cells in patients with an array of lymphoid malignancies express this receptor. In 1997, daclizumab was approved by the FDA for use in the prevention of renal allograft rejection. In addition, anti-Tac provided effective therapy for select patients with T-cell malignancies and an array of inflammatory autoimmune disorders. Finally, therapy with this antibody armed with (90)Y has led to clinical responses in the majority of patients with adult T-cell leukemia. These insights concerning the IL-2/IL-2 receptor system facilitated the development of effective daclizumab antibody therapy for select patients with leukemia/lymphoma.
Waldmann
T A
TA
Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-1374, USA. tawald@helix.nih.gov
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D007167:Immunotherapy; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007938:Leukemia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008223:Lymphoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D011868:Radioisotopes / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; D011868:Radioisotopes; D000077561:Daclizumab