Abstract
Fusion toxins are recombinant hybrid proteins composed of sequences encoding a targeting ligand, such as a growth factor, and those encoding fragments of a toxin, typically diphtheria toxin or Pseudomonas exotoxin [1,2]. These single-chain polypeptides are built upon a product template contained within each toxin molecule. The toxin molecule has three functional domains: (1) the receptor binding domain or targeting ligand recognizes and attaches the molecule to cell surface receptors, (2) the membrane translocation domain functions like a molecular syringe to release the toxic fragment into the cell cytosol, and (3) the toxic domain, which kills target cells by ADP ribosylation of elongation factor 2 and subsequent inhibition of protein synthesis. Genetic replacement of the native receptor binding domain of diphtheria toxin or Pseudomonas exotoxin A with either a eukaryotic cell receptor-specific growth factor or a peptide hormone sequence has resulted in the creation of a new class of targeted biological therapeutics that can target specific cell surface receptors on malignant or other disease-causing cells.
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Woodworth, T.G., Nichols, J.C. (1993). Recombinant fusion toxins — A new class of targeted biologic therapeutics. In: Rosen, S.T., Kuzel, T.M. (eds) Immunoconjugate Therapy of Hematologic Malignancies. Cancer Treatment and Research, vol 68. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3076-3_8
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DOI: https://doi.org/10.1007/978-1-4615-3076-3_8
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