Enhancement of immunotoxin activity using chemical and biological reagents

One of the major discoveries of effective therapeutics is the use of targeted treatment, such as antibody-directed toxins, i.e. immunotoxins; however, this medicine delivery strategy is still at a developmental stage. A number of problems need to be resolved; one is their inefficacy when applied in vivo. Research has stimulated interest in this area through the use of chemical reagents and other moieties to increase the activity of immunotoxins. In this article, reagents that can potentiate the cytotoxicity of immunotoxins are reviewed and the mechanisms that increase activity of immunotoxins are discussed. Lysosomotropic amines, especially ammonium chloride and chloroquine, may raise the pH value of the lysosome in which the conjugates enter. Carboxylic ionophores, e.g. monensin, can influence Golgi vacuolation, which may facilitate the routing of conjugates, augmenting activity. Calcium channel antagonists may increase immunotoxin killing through morphological or other mechanisms that are not yet well understood. Viral particles and surface structure can enhance the cytotoxicity of conjugates, probably through the mechanism of disrupting endosomes. In addition, cytokines, beta-adrenergic blockers, immunosuppressive agents (cyclosporin A) and some antibiotics (daunorubicin) can be used to increase the effect of immunotoxins.