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Interleukin‐2 Fusion Toxin: Targeted Therapy for Cutaneous T Cell Lymphoma
Author(s) -
FOSS FRANCINE M.
Publication year - 2001
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2001.tb03720.x
Subject(s) - diphtheria toxin , lymphoma , monoclonal antibody , fusion protein , cancer research , immunotoxin , t cell , immunology , cutaneous t cell lymphoma , cytotoxicity , in vivo , antibody , medicine , in vitro , biology , immune system , toxin , mycosis fungoides , microbiology and biotechnology , gene , biochemistry , recombinant dna
A bstract : 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. DAB 389 IL‐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. DAB 389 IL‐2 and its predecessor, DAB 486 IL‐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 .