Denileukin diftitox: a biotherapeutic paradigm shift in the treatment of lymphoid-derived disorders.
Denileukin diftitox (Ontak) represents an example of a fused molecule that targets cells bearing high affinity interleukin-2 receptors internalized via receptor-mediated endocytosis in an acidified vesicle. Denileukin diftitox is proteolytically cleaved within the endosome liberating the enzymatically active portion of the diphtheria toxin, the A fragment. Diphtheria toxin fragment A is released into the cytosol inhibiting the protein synthesis through the ADP-ribosylation of the elongation factor-2, and leading to cell death. This review focuses on the clinical trials that led to the FDA approval of the drug for cutaneous T cell lymphoma in the US, and investigational studies demonstrating drug-activity against B and T-cell non-Hodgkin's lymphoma, chronic lymphocytic lymphoma and acute graft versus disease within allogeneic hematopoietic stem cell transplant.
Turturro
Francesco
F
Feist-Weiller Cancer Center, 1501 Kings Highway, Shreveport, LA 71103, USA. fturtu@lsuhsc.edu
D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004167:Diphtheria Toxin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000628:therapy; D006801:Humans; D007376:Interleukin-2 / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000628:therapy; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use; D012449:Safety; D014481:United States; D014486:United States Food and Drug Administration
D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox