This research will determine the potential utility of novel high molecular weight iron chelators as anti cancer agents or adjuncts to other iron depriving therapeutic strategies in the treatment of cancer. This approach takes advantage of the elevated iron requirements of many types of tumors. A series 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 activity in vitro. Subsequently, in vivo efficacy will be determined in animal models of various cancers to determine relative anti tumor activity. These macromolecualr iron chelators will also be used in conjunction with antibodies directed against the transferrin receptor, as a means of interruptin the cellular 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 be significantly enhaneced with macromolecular deferoxamine conjugates which permit the maintenance of high vascular chelator concentrations. Finally, these macromolecularchelators will be tested as adjuncts to cancer therapy with gallium transferrin, a technique known to inihbit tumor growth in mice via iron deprivation.Commercial ApplicationsWe are uniquely positioned to explore macromolecualr iron chelators as anti neoplastic agents. BMF manufactures hydroxyethyl starch deferoxamine conjugates under GMP conditions and has submitted an Investigational New DRug (IND) application with the FDA for the treatment of severe burn injury. If the anti cancer studies are successful, commercialization will be straightforward and pursued aggressively.National Cancer Institute (NCI)
