Toxin-Based Therapeutic Approaches

Shapira, Assaf; Benhar, Itai

Treating cancer and chronic viral infections are among the most challenging goals in modern medicine. The recent integration of modified plant and bacterial toxins based therapies (and particularly immunotoxins with anti-tumor activity) into clinical research and application adds new weapons to the arsenal against these refractory diseases. Cumulative knowledge about toxins' structure and mechanism of action, as well as recent progress and breakthroughs in the fields of cell biology, immunology, virology, molecular biology and nanotechnology, enabled the development of different targeting strategies that are crucial for converting a lethal toxin into a therapeutic agent (see Figure 1 ). However, clinical application of engineered toxins still faces many challenges. Two major problems associated with systemic administration of immunotoxins are: 1. lack of specificity resulting from the presence of the target antigen/receptor also being present on healthy tissue ("target dependent toxicity"); 2. Undesired intoxication of healthy tissue due to the immunotoxin binding to cell surface components rather than specifically to its target antigen/receptor ("target independent toxicity"). Whereas the first problem directly relates to the target and its expression/body-distribution profile; the second relates to the nature of the therapeutic agent itself.