HAUKE LILIE:  FRIDAY 31 MARCH 2006, 11:50

Design of immunotoxins using a novel strategy to couple antibody fragment and toxin

Martin Kleinschmidt, Florian Kurschus, Dieter Jenne, Rainer Rudolph & Hauke Lilie
Institute of Biotechnology, Martin-Luther-University Halle-Wittenberg, Germany

Immunotoxins are genetically engineered fusion proteins of an antibody Fv fragment and a toxin from bacteria or plants, which function as anti-cancer therapeutics. Here we describe a new generation of immunotoxins in which both proteins do not form a single fusion protein but are coupled specifically via cysteine-containing polyionic fusion peptides. The engineered Pseudomonas exotoxin PE38 was N-terminally fused to the peptide E 8 C. In combination with the disulfide-stabilized Fv fragment of the tumor-specific antibody B3, which was extended by the peptide R 8 CP, the fusion peptides ensured a specific and covalent interaction of the Fv fragment and the toxin. The resulting immunotoxin was as active and as specific as an immunotoxin composed of the same antibody fragment and toxin which were fused genetically. Similarly, another functional immunotoxin was constructed using the apoptosis-inducing protease granzyme B as toxic component.

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