Interleukin-2 fusion toxin: targeted therapy for cutaneous T cell lymphoma

Ann N Y Acad Sci. 2001 Sep;941:166-76. doi: 10.1111/j.1749-6632.2001.tb03720.x.


The interleukin (IL)-2 receptor has proved an attractive target for T cell-directed therapies. Agents including monoclonal antibodies, single-chain antibody immunoconjugates, radioimmunoconjugates, and, most recently, ligand fusion toxins have demonstrated activity in vitro and in clinical trials in both hematologic malignancies and diseases characterized by proliferation of activated T cells, such as graft-versus-host disease. DAB389IL-2 (ONTAK) is a ligand fusion toxin consisting of the full-length sequence of the IL-2 gene genetically fused to the enzymatically active and translocating domains of diphtheria toxin. DAB389IL-2 and its predecessor, DAB486IL-2, have demonstrated activity in a variety of diseases, including cutaneous T cell lymphoma (CTCL), psoriasis, rheumatoid arthritis, and HIV infection. Further clinical development of IL-2 fusion toxins in CTCL and other hematopoietic malignancies is predicated on identification of the high-affinity IL-2 receptor complex on the malignant cells and on a better understanding of the biological determinants of cytotoxicity of these molecules in vivo.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Clinical Trials, Phase III as Topic
  • Diphtheria Toxin / adverse effects
  • Diphtheria Toxin / pharmacology
  • Diphtheria Toxin / therapeutic use*
  • Humans
  • Immunotoxins / adverse effects
  • Immunotoxins / pharmacology
  • Immunotoxins / therapeutic use*
  • Interleukin-2 / adverse effects
  • Interleukin-2 / pharmacology
  • Interleukin-2 / therapeutic use*
  • Lymphoma, T-Cell, Cutaneous / drug therapy*
  • Lymphoma, T-Cell, Cutaneous / metabolism
  • Protein Isoforms / metabolism
  • Receptors, Interleukin-2 / metabolism
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / pharmacology
  • Recombinant Fusion Proteins / therapeutic use*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / metabolism
  • Treatment Outcome


  • Antineoplastic Agents
  • DAB(486)-interleukin 2
  • Diphtheria Toxin
  • Immunotoxins
  • Interleukin-2
  • Protein Isoforms
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins
  • denileukin diftitox