Improved immunotoxins with novel functional elements.

Immunotoxins (ITs) are protein-based drugs combining a target-specific binding domain (usually derived from an antibody) and a cytotoxic domain to kill target cells. They are among the most promising new therapeutic tools to fight cancer, and several clinical trials have been completed with encouraging results. Although the targeted elimination of malignant cells is an elegant concept, there are numerous practical challenges that limit the clinical use of ITs, including inefficient cellular uptake, low cytotoxicity and off-target effects. Here we present some of the strategies that have been developed to improve the efficacy of ITs, particularly those involving the incorporation of functional peptide sequences into recombinant ITs to improve target binding, modify plasma half life and distribution, boost tumor penetration, enhance cellular uptake and increase cytotoxic efficiency.