The Use of Radioimmunotherapy in Combination with Bioreductive Agents

Abstract

Clinical trials of radiolabeled antibody therapy have produced some complete and partial responses, primarily in lymphomas (DeNardo et al. 1988; Vriesendorp et al. 1989; Press et al. 1993). However, in solid tumors, very few tumors have responded to radioimmunotherapy (RIT) alone (Order et al. 1988; Meredith et al. 1992; Breitz et al. 1992). This may be due to a number of factors including antigenic heterogeneity, inherently radioresistant tumor cells, poor antibody penetration due to factors such as interstitial hypertension and large tumor volumes, and poor tumor to normal tissue ratios limiting the dose of activity that can be injected. It has become clear that more effective strategies must be developed which will minimize these factors that are preventing adequate tumor treatment. One possibility is to combine RIT with bioreductive agents which are drugs that are activated under reducing conditions in vivo, as are found in the hypoxic regions of tumors.