Immunotoxins

Immunotoxins are molecules which contain a protein toxin connected to a targeting antibody. The goal of therapy is for the molecule to bind selectively to cancer cells, or to cells mediating autoimmune disease, internalise and then for the toxin to kill the cell. Several immunotoxins meeting this definition are in preclinical and clinical development, but none are approved yet for use in general practice. One close relative of immunotoxins is the growth factor fusion toxin, wherein the targeting antibody is replaced with a growth factor that selectively binds and this ligand is fused in a recombinant fashion to a protein toxin. One such molecule, containing human interleukin-2 (IL-2) fused to truncated diphtheria toxin (DT), has recently been approved under the name Ontak, and others are under development. A newer class of immunotoxins, termed recombinant immunotoxins, contain the variable or antigen binding domains of an antibody fused in recombinant fashion to a toxin. Recombinant immunotoxins, like growth factor fusion toxins, can be produced efficiently from bacteria and have a defined structure with respect to the linkage between the toxin and the ligand. However, they can, like conventional immunotoxins, be directed to antigens other than growth factor receptors, including receptor subunits. Several recombinant immunotoxins are under clinical testing and major responses have been reported, particularly in haematological malignancies. Some of these molecules may enter clinical practice in the future as targeted therapy, which is a modality distinct from those of chemotherapy, surgery and radiation therapy.