Immunotoxins: experimental design

One of the major goals of tumor immunotherapy is to overcome immune escape and tumor anergy mechanisms. The identification of (relatively) tumor-specific epitopes is more important for adoptive immunotherapy strategies than their immunogenicity. In the immunocellular approach, D44v-epitope-specific T-cells were cloned introducing a fusion gene encoding the single chain Fv-fragment of CD44v-specific mAb and the zeta-chain of the TCR complex. MHC-independent retargeted cytotoxicity could be shown toward antigen-expressing tumor cells in vitro and in vivo. In a humoral approach, the fusion gene for a Her2neu-specific scFv and a bacterial toxin was expressed in E coli. After purification the fusion toxin showed significant activity in animal experiments using Her2-neu-expressing tumors. Meanwhile, the first six patients suffering from Her2-neu-expressing cancers have been treated topically so far. No significant systemic or local side effects could be detected. Four out of six patients had a local PR/CR. Further clinical studies are warranted and ongoing.