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Taming ricin toxin

Nature Biotechnology volume 21, pages 372–374 (2003)Cite this article

An immunotoxin is made safer by the introduction of a point mutation.

Ricin is a potent toxin once famously delivered on the tip of an umbrella to assassinate a bothersome Bulgarian journalist. Ricin's cytocidal properties have also been exploited in cancer treatment in which the toxin is hooked up to antibodies that specifically target tumor cells. Such immunotoxin conjugates have not yet reached their full potential in the clinic because of 'vascular leak syndrome,' a side effect resulting from endothelial damage that causes fluid to escape from the bloodstream into the lungs, muscle, brain, and other tissues. In this issue, Vitetta and colleagues1 show that a single point mutation in ricin toxin can eliminate vascular leak syndrome without compromising the toxin's enzymatic action. Moreover, they construct a mutant immunotoxin that is tolerated at higher doses in mice and thereby leads to improved antitumor activity.

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Figure 1: The recombinant A chain of ricin toxin is missing the B domain needed to bind to cells, but can be directed to kill cancer cells by connecting it to a monoclonal antibody that binds to a tumor antigen.

References

  1. Smallshaw, J.E. et al. Nat. Biotechnol. 21 387–391 (2003).

    CAS  Article  Google Scholar 

  2. Amlot, P.L. et al. Blood 82, 2624–2633 (1993).

    CAS  PubMed  Google Scholar 

  3. Sausville, E.A. et al. Blood 85, 3457–3465 (1995).

    CAS  PubMed  Google Scholar 

  4. Baluna R., Rizo J., Gordon B.E., Ghetie V. & Vitetta E.S. Proc. Natl. Acad.of Sci. USA 96, 3957–3962 (1999).

    CAS  Article  Google Scholar 

  5. Baluna R., Coleman E., Jones C., Ghetie V. & Vitetta E.S. Exp. Cell. Res. 258, 417–424 (2002).

    Article  Google Scholar 

  6. Fulton R.J., Tucker T.F., Vitetta E.S. & Uhr J.W. Cancer Res. 48, 2618–2625 (1988).

    CAS  PubMed  Google Scholar 

  7. Thorpe P.E. et al. Cancer Res. 48, 6396–6403 (1988).

    CAS  PubMed  Google Scholar 

  8. Olsen E. et al. J. Clin. Oncol. 19, 376–388 (2001).

    CAS  Article  Google Scholar 

  9. Kreitman R.J. et al. New. Engl. J. Med. 345, 241–247 (2001).

    CAS  Article  Google Scholar 

  10. Kreitman R.J. et al. J. Clin. Oncol. 18, 1614–1636 (2000).

    Article  Google Scholar 

  11. Frankel A.E., Powell B.L., Hall P.D., Case L.D. & Kreitman R.J. Clin. Cancer Res. 8, 1004–1013 (2002).

    CAS  PubMed  Google Scholar 

  12. Kuan C., Pai L.H. & Pastan I. Clin. Cancer Res. 1, 1589–1594 (1995).

    CAS  PubMed  Google Scholar 

Download references

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  1. chief of the Division of Cancer Biology, Clinical Immunotherapy Section, Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, 20892-4255, MD

    Robert J. Kreitman

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  1. Robert J. Kreitman
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Kreitman, R. Taming ricin toxin. Nat Biotechnol 21, 372–374 (2003). https://doi.org/10.1038/nbt0403-372

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  • DOI: https://doi.org/10.1038/nbt0403-372

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