lron deprivation and cancer: a view beginning with studies of monoclonal antibodies against the transferrin receptor

Abstract

This review provides a perspective on the potential utility of iron deprivation treatments as components of cancer therapy. The perspective began to develop with investigations of the selective inhibitory effects on lymphocyte activation which were produced by rnonoclonal antibodies against the transferrin receptor. Those investigations led to the unexpected discovery that such antibodies would produce synergistic inhibition of lymphoid tumor growth in vitro when used in combination with the iron chelator deferoxamine. The perspective was further developed whea additional studies in vivo indicated that combination iron deprivation treatrnent could prevent initial tumor outgrowth and cause regressions of established tumors in the 38C13 rnurine lymphorna model. The anti-tumor effects were accompanied by significant toxicities, however, and the analysis of the causes of those toxicities is now an irnportant issue. The opportunities and problerns which these results present are interpreted in the broader context of currently available information conceming the anti-tumor effects of deferoxamine and gallium nitrate in the pre-clinical and clinical settings, and questions for future research are presented.