A STRATEGY FOR SPECIFIC TARGETING OF THERAPEUTIC AGENTS TO TUMOR-CELLS OF VIRUS-ASSOCIATED CANCERS

Expression of viral genes in tumour cells of the virus-associated canc ers could provide highly selective ways of targeting expression of the rapeutic vectors to the tumour cells. The ubiquitous presence of EBNA- 1 in Epstein-Barr virus associated cancers could be used to activate e xpression constructs containing oriP in the tumour cells. This is demo nstrated for a variety of model system including epithelial, cells whi ch would be the target cell type for the treatment of undifferentiated nasopharyngeal carcinoma, a cancer that always contains Epstein-Bar v irus in the tumour cells. Combining an oriP/EBNA-1-dependent Epstein-B arr virus Cp promoter with delayed assay of reporter gene, a 108-fold differential was obtained between the activity of a transfected plasmi d in cells containing or lacking EBNA-1 expression. This might provide sufficient specificity for a successful in vivo therapeutic strategy.