Abstract
Recombinant immunotoxins are chimeric proteins composed of the Fv portion of a monoclonal antibody (MAb) fused to a portion of a toxin. The Fv replaces the cell-binding domain of the toxin and directs the toxin to cancer cells that express a target antigen. There are several features that make toxins attractive agents designed to kill cancer cells. They are very potent, and they are able to kill cells that are resistant to standard chemotherapy. Recombinant immunotoxins (RITs) have been produced that kill different types of cancer cells, as well as human immunodeficiency virus (HIV)-infected cells, taking advantage of gp120 on the surface of HIV-infected cells.
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References
Hwang, J., FitzGerald, D.J.P., Adhya, S., and Pastan, I. (1987) Functional domains of pseudomonas exotoxin identified by deletion analysis of the gene expressed in E. coli. Cell 48, 129–136.
Keppler-Hafkemeyer, A., Brinkmann, U., and Pastan, I. (1998) Role of caspases in immunotoxin-induced apoptosis of cancer cells. Biochemistry 45, 16,934–16,942.
Kreitman, R. J., Wilson, W. H., Bergeron, K., Raggio, M., Stetler-Stevenson, M., FitzGerald, D. J., et al. (2001) Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant Hairy-cell leukemia. N. Engl. J. Med. 345, 241–247.
Kreitman, R. J., Wilson, W. H., White, J. D., Stetler-Stevenson, M., Jaffe, E. S., Giardina, S., et al. (2000) Phase I trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies. J. Clin. Oncol. 18, 1622–1636.
Benhar, I., Reiter, Y., Pai, L. H., and Pastan, I. (1995) Administration of disulfide-stabilized Fv-immunotoxins B1(dsFv)-PE38 and B3(dsFv)-PE38 by continuous infusion increases their efficacy in curing large tumor xenografts in nude mice. Int. J. Cancer 62, 351–355.
Onda, M., Nagata, S., Tsutsumi, Y., Vincent, J. J., Wang, Q-C., Kreitman, R. J., et al. (2001) Lowering the isoelectric point of the Fv portion of recombinant immunotoxins leads to decreased nonspecific animal toxicity without affecting antitumor activity. Cancer Res. 61, 5070–5077.
Brinkmann, U., Reiter, Y., Jung, S.-H., Lee, B., and Pastan, I. (1993) A recombinant immunotoxin containing a disulfide-stabilized Fv fragment (dsFv). Proc. Natl. Acad. Sci. USA 90, 7538–7542.
Studier, F. W. and Moffatt, B. A. (1986) Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes. J. Mol. Biol. 189, 113.
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© 2004 Humana Press Inc., Totowa, NJ
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Pastan, I., Beers, R., Bera, T.K. (2004). Recombinant Immunotoxins in the Treatment of Cancer. In: Lo, B.K.C. (eds) Antibody Engineering. Methods in Molecular Biology™, vol 248. Humana Press. https://doi.org/10.1385/1-59259-666-5:503
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DOI: https://doi.org/10.1385/1-59259-666-5:503
Publisher Name: Humana Press
Print ISBN: 978-1-58829-092-2
Online ISBN: 978-1-59259-666-9
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