Enhanced pancreatic tumor regression by a combination of adenovirus and retrovirus-mediated delivery of the herpes simplex virus thymidine kinase gene

We have evaluated the effectiveness of combining the different characterist ics of retrovirus and adenovirus to apply the herpes simplex Virus thymidin e kinase gene (HSVtk) and ganciclovir (GCV) treatment for gene therapy of p ancreatic cancer. Transduction of NP-18 human pancreatic cells in culture b y either the adenoviral vector (ADV/tk) or the retroviral vector (Rv/tk) fo llowed by GCV treatment resulted in a GCV dose-dependent cytotoxic effect. A bystander effect was determined both in NP-18 cultures and in xenogeneic cell mixtures of NP-18 and PA317 cells. Studies in vivo indicated that the effectiveness of tumor regression after HSVtk gene transfer and GCV treatme nt was dependent first an the tumor size at the time of viral injection and secondly, in large tumors, on the type of virus administered. The administ ration of the viral combination (ADV/tk + vector producer cells VPC-Rv/tk) was the best approach tested and resulted in a dramatic reduction in tumor mass after 4 days of GCV treatment which was maintained for the treatment p eriod. Remarkably, two animals presented a complete eradication of the tumo r Thus, the HSVtk/GCV system when administered using a viral combination (A DV/tk + VPC-Rv/tk), may be a promising suicide gene therapy for pancreatic carcinomas.