A strategy for specific targeting of therapeutic agents to tumour cells of virus-associated cancers.
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.
Evans
T J
TJ
Ludwig Institute for Cancer Research, Imperial College School of Medicine at St Mary's, London, UK.
Brooks
L
L
Farrell
P J
PJ
D002051:Burkitt Lymphoma / Q000628:therapy* / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics*; D015870:Gene Expression; D018390:Gene Targeting; D004854:Herpesvirus 4, Human; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000628:therapy* / Q000821:virology; D010957:Plasmids
D019309:Epstein-Barr Virus Nuclear Antigens