Recombinant toxins in haematologic malignancies and solid tumours.
Recombinant toxins constitute a new modality for the treatment of cancer, since they target cells displaying specific surface-receptors or antigens. They are fusion proteins, which contain toxin and ligand regions, and are produced in Escherichia coli. The ligand may be a growth factor or a fragment of an antibody, and the toxin is usually one of the two bacterial toxins: Pseudomonas exotoxin and diphtheria toxin. Compared to the earlier generation chemical conjugates of ligands and toxins, recombinant toxins have many advantages, including homogeneity with respect to the connection between the ligand and toxin, ease and yield of production and small size. A variety of chemotherapy-resistant haematologic and solid tumours have been targeted with recombinant toxins, and clinical trials with many of them have recently demonstrated their effectiveness. Moreover, their unwanted toxic effects are different from those of most chemotherapeutic agents, supporting the expectation that they can be combined with existing modalities to improve the clinical resources available to treat cancer in humans.
Division of Cancer Biology, National Cancer Institute, National Institutes of Health, 37/4B27, 37 Convent Drive, MSC 4255, Bethesda, MD 20892, USA.
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Kreitman