Gene Therapy (2000) 7, 255--262

Introduction Macrophages can form a significant proportion of the solid tumour mass and consequently play an important role in tumour progression. The role of macrophages in tumorigenesis remains controversial as they can display both a growth promoting as well as a tumoricidal phenotype. 2,3 The tumoricidal properties of macrophages have been exploited in human cancer therapy. Clinical protocols involve the transfer of patient-derived macrophages that have been matured and activated with IFN# ex vivo before administration. To date these studies have reported only a few side-effects, such as low grade fevers and chills. However despite localisation, minimal efficacy was observed implying that activated macrophages per se are not potent enough to mediate significant therapeutic activity. The strategy we describe here aims to remedy this by `arming' macrophages with a therapeutic gene to effect gene dependent enzyme prodrug therapy (GDEPT). In this way a non-toxic enzyme ca