Human toxin-based recombinant immunotoxins/chimeric proteins as a drug delivery system for targeted treatment of human diseases.

INTRODUCTION: The development of specific immunosuppressive reagents remains the major goal in the treatment of human diseases. One such approach is the use of recombinant immunotoxins/chimeric proteins, composed of targeting and killing moieties, fused at the cDNA level. Most of these 'magic bullets' use bacterial or plant toxins to induce cell death. These toxins are extremely potent, but they also cause severe toxicity and systemic side effects that limit the maximal doses given to patients. Moreover, being of non-human origin, they are highly immunogenic, and the resulting neutralizing antibody production impairs their efficacy. AREAS COVERED: This review describes recombinant immunotoxins/chimeric proteins composed of the classical delivering, cell-targeting molecules, fused to highly cytotoxic human proteins capable of generating an intense apoptotic response within the target cell. This review focuses on the new 'Human Killing Moieties' of these targeted proteins and describes recent progress in the development of these promising molecules. EXPERT OPINION: Human toxin-based immunotoxins/chimeric proteins for the targeted delivery of drugs are still in their early stages of development. However, they are certain to advance in the very near future to become an extra weapon in the everlasting war against human diseases, mainly cancer.