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Immunotoxin
From Wikipedia, the free encyclopedia
An immunotoxin is a human-made protein that consists of a targeting portion linked to a toxin. When the protein binds to that cell, it is taken in through endocytosis, and the toxin kills the cell.[1] They are used for the treatment of some kinds of cancer and a few viral infections.
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[edit] Design
These chimeric proteins are usually made of a modified antibody or antibody fragment, attached to a fragment of a toxin. The targeting portion is composed of the Fv portion of an antibody that targets a specific cell type.[2] The toxin is usually a cytotoxic protein derived from a bacterial or plant protein, from which the natural binding domain has been removed so that the Fv directs the toxin to the antigen on the target cell.[1]
Sometimes recombinant fusion proteins containing a toxin and a growth factor are also referred to as recombinant immunotoxins, although though they do not contain an antibody fragment. A more specific name for this latter kind of protein is recombinant fusion toxin.
[edit] Production
They were originally produced by attaching the antibody to the toxin using a chemical linker. They are now made using recombinant DNA techniques, are produced in bacteria like E. coli and are called recombinant immunotoxins.
[edit] Function
The antibody (or other targeting moiety) binds to an antigen on the target cell and the toxin then enters and kills the cell.
[edit] Clinical application
The best clinical success has been achieved in treating patients with refractory hairy cell leukemia.[citation needed] These patients were treated with the recombinant immunotoxin, BL22, which targets the CD22 cell surface receptor, which is highly expressed on these leukemic cells. In two uncontrolled clinical studies, about half of participants achieved a complete response after BL22 treatment.[3] This therapeutic has been superseded by HA22, a slightly modified version.
[edit] See also
- Denileukin diftitox, an immunotoxin used to treat T cell leukemias
- Anti-CD22 immunotoxins, being tested in hairy cell leukemia
[edit] References
- ^ a b Pastan I, Hassan R, FitzGerald DJ, Kreitman RJ (2007). "Immunotoxin treatment of cancer". Annu. Rev. Med. 58: 221–37. doi:. PMID 17059365.
- ^ Pastan I, Hassan R, Fitzgerald DJ, Kreitman RJ (July 2006). "Immunotoxin therapy of cancer". Nat. Rev. Cancer 6 (7): 559–65. doi:. PMID 16794638.
- ^ Kreitman RJ, Wilson WH, Bergeron K, et al (July 2001). "Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia". N. Engl. J. Med. 345 (4): 241–7. doi:. PMID 11474661. http://content.nejm.org/cgi/pmidlookup?view=short&pmid=11474661&promo=ONFLNS19.