Recombinant immunotoxins for the treatment of haematological malignancies.
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), 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.
Kreitman
Robert J
RJ
Clinical Immunotherapy Section, Laboratory of Molecular Biology, Centers for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 5124b, Bethesda, MD 20892-4255, USA. kreitmar@mail.nih.gov
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005544:Forecasting; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007128:Immunoglobulin Fragments / Q000008:administration & dosage / Q000627:therapeutic use; D000922:Immunotoxins / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D008252:Macaca fascicularis; D051379:Mice; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012074:Remission Induction; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D007128:Immunoglobulin Fragments; D000922:Immunotoxins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins