A strategy for specific targeting of therapeutic agents to tumour cells of virus-associated cancers

Abstract

Expression of viral genes in tumour cells of the virus-associated cancers could provide highly selective ways of targeting expression of therapeutic vectors to the tumour cells. The ubiquitous presence of EBNA-1 in Epstein–Barr virus-associated cancers could be used to activate expression constructs containing oriP in the tumour cells. This is demonstrated for a variety of model systems including epithelial cells, which would be the target cell type for the treatment of undifferentiated nasopharyngeal carcinoma, a cancer that always contains Epstein–Barr virus in the tumour cells. Combining an oriP/EBNA-1-dependent Epstein–Barr virus Cp promoter with delayed assay of reporter gene, a 108-fold differential was obtained between the activity of a transfected plasmid in cells containing or lacking EBNA-1 expression. This might provide sufficient specificity for a successful in vivo therapeutic strategy.