IMMUNOLIPOSOMES BEARING ENZYMES (IMMUNO-ENZYMOSOMES) FOR SITE-SPECIFIC ACTIVATION OF ANTICANCER PRODRUGS

Immunoliposomes bearing anticancer prodrug activating enzymes (immuno- enzymosomes) are proposed for use in a two-phase approach to targeted chemotherapy of human cancer. In the first phase the tumor-specific im muno-enzymosomes are administered, and time is allowed for tumor local ization and clearance from blood and other tissues. The second phase i nvolves the administration of a nontoxic prodrug which is converted to a cytotoxic drug by the action of the tumor cell-bound immuno-enzymos omes. This approach is a modified form of antibody-directed enzyme pro drug therapy (ADEPT). This contribution briefly summarizes our current efforts to develop this new application for liposomes in cancer thera py. The enzyme beta-glucuronidase (GUS), capable of activating anthrac ycline-prodrugs, was coupled to the external surface of immunoliposome s directed against ovarian carcinoma cells. These immuno-enzymosomes w ere tested in vitro for their enzymatic activity, stability, target ce ll binding capability and prodrug-activating capacity. The potential a nd limitations of the immuno-enzymosome concept are discussed.