Immunotoxins, genetically engineered

Ricin is a type II toxin. The A chain (ricin A) contains 267 amino acid residues, and the B chain (ricin B) 262 residues. Ricin A is exceptionally toxic, and it has been estimated that a single molecule is sufficient to kill an individual cell. This peptide can be prepared by genetic engineering using Escherichia coli. The potent action of this material on eukaryotic cells has been investigated in anticancer therapy. Ricin A has been coupled to monoclonal antibodies and successfully delivered specifically to the tumour cells. However, in vitro toxicity of ricin A-based immunotoxins is enhanced significantly if ricin B is also present. 

Smallshaw JE, Ghetie V, Rizo J, Fulton JRJ, Trahan L, Ghetie MA, Vitetta E. Genetic engineering of an immunotoxin to eliminate pulmonary vascular leak in mice. Nat Biotechnol 2003 21 387-91. 

In addition to the constructs described above, a number of genetically engineered fusion proteins with antibodies has been described [Sen ter and Springer, 2001]. Antibody fusion proteins are made byreplacing a part of the antibody molecule with a fusion partner, such as an enzyme or a toxin that confers a novel function to the antibody. In some cases, such as immunotoxins, the variable regions of the antibody are retained in order to retain antigen binding and specificity, while the constant domains are deleted and... 

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