TARGETED CHEMOTHERAPY BY INTRATUMOR INJECTION OF ENCAPSULATED CELLS ENGINEERED TO PRODUCE CYP2B1, AN IFOSFAMIDE ACTIVATING CYTOCHROME-P450

The prognosis of pancreatic adenocarcinoma is poor and current treatme nt ineffective. A novel treatment strategy is described here using a m ouse model system for pancreatic cancer. Cells that have been genetica lly modified to express the cytochrome P450 2B1 enzyme are encapsulate d in cellulose sulphate and implanted into pre-established tumours der ived from human pancreatic cells. Cytochrome P450 2B1 converts the che motherapeutic agent ifosfamide to toxic metabolites. Administration of ifosfamide to tumour-bearing mice that were recipients of implanted e ncapsulated cells results in partial or even complete tumour ablation. These results suggest that in situ chemotherapy with genetically modi fied cells in an immunoprotected environment may prove useful for appl ication in man.