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A recombinant immunotoxin consisting of two antibody variable domains fused to Pseudomonas exotoxin

Abstract

ANTIBODIES and growth factors have been chemically coupled to different toxins to produce cytotoxic molecules that selectively kill cells bearing appropriate antigens or receptors1,2. Antibody-toxin conjugates (immunotoxins) produced using conventional chemical coupling techniques have several undesirable characteristics. The smallest binding unit of an antibody is an Fv fragment which consists of a light and heavy chain variable domain. Recently, active single chain Fv fragments of antibodies have been produced in Esherichia coli x by attaching the light and heavy chain variable domains together with a peptide linker3,4. Here we describe the construction and expression in E coli. of a single chain antibody toxin fusion protein, anti-Tac(Fv)–PE40, in which the variable regions of anti-Tac, a monoclonal antibody to the p55 subunit of the human interleukin-2 receptor5, are joined in peptide linkage to PE40, a modified form of Pseudomonas exotoxin lacking its binding domain. Anti-Tac(Fv)–PE40 was very cytotoxic to two interleukin-2 receptor-bearing human cell lines but was not cytotoxic to receptor-negative cells.

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Chaudhary, V., Queen, G., Junghans, R. et al. A recombinant immunotoxin consisting of two antibody variable domains fused to Pseudomonas exotoxin. Nature 339, 394–397 (1989). https://doi.org/10.1038/339394a0

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