Tumor Growth Inhibition by Iron Deprivation

This research will determine the potential utility of novel high molecular weight iron chelatorsas anti-cancer agents or adjuncts to other iron-depriving therapeutic strategies in the treatment ofcancer. This approach takes advantage of the elevated iron requirements of many types of tumors. Aseries of high molecular weight iron chelators consisting of the powerful iron-binding drug, deferoxamine(DFO), coupled to biocompatible polymers will be synthesized and screened for anti-neoplastic activityin vitro. Subsequently, in vivo efficacy will be determined in animal models of various cancers todetermine relative anti-tumor activity. These macromolecualr iron chelators will also be used inconjunction with antibodies directed against the transferrin receptor, as a means of interruptin thecellular iron acquisition system. It has been shown previously that the combination of DFO and anti-transferrin recepto antibodies (ATRAs) provides synergistic anti-tumor activity. This effect may besignificantly enhaneced with macromolecular deferoxamine conjugates which permit the maintenanceof high vascular chelator concentrations. Finally, these macromolecular chelators will be tested asadjuncts to cancer therapy with gallium-transferrin, a technique known to inihbit tumor growth in micevia iron deprivation.