Journal
EXPERT OPINION ON BIOLOGICAL THERAPY
Volume 4, Issue 7, Pages 1115-1128Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/14712598.4.7.1115
Keywords
CD3; CD7; CD22; CD25; CD30; CD64; CD87; diphtheria toxin; fusion protein; granulocyte-macrophage colony-stimulating factor; Hodgkin's disease; IL-2; IL-3; leukaemia; lymphoma; monoclonal antibody; pseudomonas exotoxin; urokinase
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Recombinant immunotoxins are fusion proteins which contain a ligand derived from the immune system fused to a toxin. The protein toxin is truncated to delete its binding domain, allowing selective ligand-directed binding. Growth factor fusion toxins are often considered immunotoxins. One of these molecules, containing the truncated diphtheria toxin and human IL-2 (Ontak(R), Ligand Pharmaceuticals), has been approved for the treatment of cutaneous T-cell lymphoma. Recombinant immunotoxins have also been produced containing the variable domains (Fv fragment) of monoclonal antibodies fused to toxins. These agents are relatively versatile with respect to the range of antigens possible. Several of these recombinant immunotoxins have showed clinical effectiveness in Phase I testing against haematological malignancies. One of these molecules, BL22, targets CD22 on hairy-cell leukaemia and has enabled patients to achieve complete remissions despite previous treatment and resistance to chemotherapy.
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