Optimizing denileukin diftitox (Ontak) therapy.
Denileukin diftitox (Ontak) is a novel recombinant fusion protein consisting of peptide sequences for the enzymatically active and membrane translocation domain of diphtheria toxin linked to human IL-2. Denileukin diftitox specifically binds to IL-2 receptors on the cell membrane, is internalized via receptor-mediated endocytosis and inhibits protein synthesis by ADP ribosylation of elongation factor 2, resulting in cell death. This article focuses on the clinical trial that led to the US FDA approval of the drug for cutaneous T-cell lymphoma in 1999, and other investigational studies for hematologic malignancies, recurrent and refractory chronic lymphocytic leukemia, non-Hodgkin B-cell lymphoma, graft-versus-host disease and autoimmune disease, demonstrating the activity and adverse effects of the drug.
Duvic
Madeleine
M
The University of Texas MD Anderson Cancer Center, Division of Internal Medicine, Department of Dermatology, 1515 Holcombe Blvd, Unit 1452, Houston, TX 77030, USA. mduvic@mdanderson.org
Talpur
Rakhshandra
R
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D019559:Capillary Leak Syndrome / Q000139:chemically induced; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D004167:Diphtheria Toxin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy; D019337:Hematologic Neoplasms / Q000188:drug therapy; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015375:Receptors, Interleukin-2 / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D013971:Thyrotoxicosis / Q000139:chemically induced
D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007376:Interleukin-2; D011500:Protein Synthesis Inhibitors; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox