Recombinant toxins for the treatment of cancer.
Recombinant toxins are proteins made by genetic engineering consisting of a toxin fused to a ligand which binds selectively to a target cell. Recombinant toxins used for cancer treatment generally contain either a growth factor or a recombinant fragment of a monoclonal antibody fused to a truncated bacterial toxin, derived either from Pseudomonas exotoxin or from diphtheria toxin. One recombinant toxin containing human interleukin (IL)-2 and truncated diphtheria toxin (DAB389-IL-2, denileukin diftitox or Ontak; Seragen Inc) is approved for clinical use in advanced stage cutaneous T-cell lymphoma. Recombinant toxins containing truncated Pseudomonas exotoxin and fragments of anti-CD22 and anti-CD25 monoclonal antibodies have induced remissions in chemotherapy-resistant hematological malignancies, particularly hairy cell leukemia, and are currently undergoing experimental testing. The number of approved recombinant toxins for the treatment of cancer is expected to increase in the coming years.
Kreitman
Robert J
RJ
Division of Cancer Biology, National Institutes of Health, 9000 Rockville, Bethesda, MD 20892, USA. kreitmar@mail.nih.gov
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004167:Diphtheria Toxin / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D000922:Immunotoxins / Q000276:immunology / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use; D007943:Leukemia, Hairy Cell / Q000628:therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D004167:Diphtheria Toxin; D000922:Immunotoxins; D007376:Interleukin-2; D011994:Recombinant Proteins