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Immunotoxin therapy of cancer

Nature Reviews Cancer volume 6, pages 559–565 (2006)Cite this article

Abstract

Rationally designed anticancer agents that target cell-surface antigens or receptors represent a promising approach for treating cancer patients. However, antibodies that bind these targets are often, by themselves, non-cytotoxic. By attaching potent toxins we can dramatically improve the clinical utility of some anti-tumour antibodies. Here we describe the construction and clinical utility of several recombinant immunotoxins; each of which is composed of antibody Fv fragments fused to powerful bacterial toxins. Results from clinical trials indicate that recombinant immunotoxins and similar agents that are designed to combine antibody selectivity with toxin cell-killing potency will be useful additions to cancer therapy.

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Figure 1: BL22.
Figure 2: Strategy used to make single-chain or disulphide-linked immunotoxins.
Figure 3: Model of a recombinant immunotoxin.
Figure 4: DAB389IL2.

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Acknowledgements

This research was supported by the Intramural Research Program of the US National Institutes of Health, the National Cancer Institute and the Center for Cancer Research.

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  1. Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institues of Health, 37 Convent Drive, Bethesda, 20892-4264, MD, USA

    Ira Pastan, Raffit Hassan, David J. FitzGerald & Robert J. Kreitman

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  1. Ira Pastan
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Correspondence to Ira Pastan.

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Competing interests

D.J.F is a named co-inventor of the immunotoxin technology, and could benefit from patent royalties, but does not own stock in any related companies. I.P. has a patent for the use of genetically modified PE to make immunotoxins. R.J.K. is a named co-inventor on the US National Institutes of Health patent for BL22.

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National Cancer Institute

paediatric acute lymphoblastic leukaemia

chronic lymphocytic leukaemia

non-Hodgkin lymphoma

Hodgkin disease

hairy-cell leukaemia

acute myeloid leukaemia

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Pastan, I., Hassan, R., FitzGerald, D. et al. Immunotoxin therapy of cancer. Nat Rev Cancer 6, 559–565 (2006). https://doi.org/10.1038/nrc1891

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