A novel approach to cancer therapy using an oncolytic herpes virus to package amplicons containing cytokine genes

There are two promising herpes viral-based anticancer strategies: one invol ves replication-defective viruses to transfer therapeutic transgenes, and t he other involves replication-conditional oncolytic viruses, which selectiv ely infect and destroy cancer cells directly. This study examines a novel d ual herpesvirus preparation, which combines the immunostimulatory effects o f amplicon-mediated IL2 expression with direct viral-induced oncolysis. The oncolytic virus G207 was used as the helper virus to package a herpes simp lex virus (HSV)-amplicon vector carrying the gene IL2 (HSV-IL2), yielding a single preparation with two complementary modes of action. In vivo compari son was carried out in a syngeneic squamous cell carcinoma flank tumor mode l. We directly injected established tumors with HSV-IL2, G207, G207 mixed w ith HSV-IL2, or G207-packaged HSV-amplicon carrying the IL2 transgene (G207 [IL2]). Significant inhibition of tumor growth was seen at 2 weeks in the G 207[IL2]-treated tumors relative to controls (0.57 +/- 0.44 cm(3) versus 39 .45 +/- 5.13 cm(3), P < 0.00001), HSV-IL2 (20.97 +/- 4.60 cm(3)), and the G 207 group (7.71 +/- 2.10 cm(3)). This unique use of a replication-condition al, oncolytic virus to package a replication-incompetent amplicon vector de monstrates impressive efficacy in vitro and in vivo, and avoids the theoret ical concerns of recombination with reversion to wild type.