Magnetic Targeted Delivery of TNF Alpha and Melphalan

DESCRIPTION (provided by applicant): Current cancer therapy is usually systemic which results in relatively low drug concentrations at the tumor and a high rate of toxic side effects. The challenge in cancer therapy is how to deliver the therapeutic agents directly to the tumors at a high concentration and yet maintain low systemic concentrations so that side effects are reduced. FeRx proposes to evaluate the use of magnetically targeted carriers (MTCs) to deliver the highly potent therapeutic agents Tumor Necrosis Factor alpha (TNFalpha) and melphalan to solid tumors or organs. MTCs are magnetic microparticles composed of metallic iron and activated carbon capable of binding a wide variety of pharmaceutical agents. MTCs are administered via intra-arterial administration and are localized to the tumors using an externally positioned magnet. TNFalpha and melphalan are highly potent therapeutic agents against a variety of malignancies. An excellent synergistic effect has been observed when the combination of the two drugs is used to treat patients with unresectable soft tissue sarcomas using an isolated limb perfusion. This synergistic effect has also been observed in isolated liver or lung perfusion. However, the isolated organ perfusion procedure is complex, long, and dangerous for patients and, often, cannot be repeated. In order to provide a safer and more practical approach to local-regional treatment than isolated organ perfusion procedures, FeRx proposes to evaluate the MTC technology for the local delivery of TNFalpha and melphalan. FeRx proposes: 1) to optimize MTCs for the delivery of TNFalpha and melphalan; 2) to evaluate the in vitro biological activity of MTC-TNFalpha and MTC-melphalan; 3) to investigate the in vivo preliminary efficacy of the MTC drug complexes in a rat tumor model.