Immunotoxins for targeted cancer therapy.
Immunotoxins are proteins that contain a toxin along with an antibody or growth factor that binds specifically to target cells. Nearly all protein toxins work by enzymatically inhibiting protein synthesis. For the immunotoxin to work, it must bind to and be internalized by the target cells, and the enzymatic fragment of the toxin must translocate to the cytosol. Once in the cytosol, 1 molecule is capable of killing a cell, making immunotoxins some of the most potent killing agents. Various plant and bacterial toxins have been genetically fused or chemically conjugated to ligands that bind to cancer cells. Among the most active clinically are those that bind to hematologic tumors. At present, only 1 agent, which contains human interleukin-2 and truncated diphtheria toxin, is approved for use in cutaneous T-cell lymphoma. Another, containing an anti-CD22 Fv and truncated Pseudomonas exotoxin, has induced complete remissions in a high proportion of cases of hairy-cell leukemia. Refinement of existing immunotoxins and development of new immunotoxins are underway to improve the treatment of cancer.
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
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001427:Bacterial Toxins / Q000737:chemistry; D002986:Clinical Trials as Topic; D004167:Diphtheria Toxin / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D007128:Immunoglobulin Fragments / Q000378:metabolism; D000922:Immunotoxins / Q000008:administration & dosage* / Q000627:therapeutic use; D007376:Interleukin-2 / Q000737:chemistry; D007943:Leukemia, Hairy Cell / Q000188:drug therapy*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000737:chemistry
D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D004167:Diphtheria Toxin; D007128:Immunoglobulin Fragments; D000922:Immunotoxins; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D051918:Sialic Acid Binding Ig-like Lectin 2