Interleukin-2 fusion toxin: targeted therapy for cutaneous T cell lymphoma.
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.
Foss
F M
FM
Tufts New England Medical Center, Boston, Massachusetts 02111, USA. ffoss@lifespan.org
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D017326:Clinical Trials, Phase III as Topic; D004167:Diphtheria Toxin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D000922:Immunotoxins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
D000970:Antineoplastic Agents; C054780:DAB(486)-interleukin 2; D004167:Diphtheria Toxin; D000922:Immunotoxins; D007376:Interleukin-2; D020033:Protein Isoforms; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox