A Novel Approach to Cancer Therapy Using an Oncolytic Herpes Virus to Package Amplicons Containing Cytokine Genes
John F. Carew ; David A. Kooby ; Yuman Fong ; Howard J. Federoff ; Se-Heon Kim ; Marc W. Halterman
Molecular Therapy, Vol.4(3) : 250~256, 2001
There are two promising herpes viral-based anticancer strategies: one involves replication-defective viruses to transfer therapeutic transgenes, and the other involves replication-conditional oncolytic viruses, which selectively infect and destroy cancer cells directly. This study examines a novel dual herpesvirus preparation, which combines the immunostimulatory effects of amplicon-mediated IL2 expression with direct viral-induced oncolysis. The oncolytic virus G207 was used as the helper virus to package a herpes simplex virus (HSV)-amplicon vector carrying the gene IL2 (HSV-IL2), yielding a single preparation with two complementary modes of action. In vivo comparison was carried out in a syngeneic squamous cell carcinoma flank tumor model. We directly injected established tumors with HSV-IL2, G207, G207 mixed with 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 G207[IL2]-treated tumors relative to controls (0.57plusminus0.44 cm3 versus 39.45plusminus5.13 cm3, P <0.00001), HSV-IL2 (20.97plusminus4.60 cm3), and the G207 group (7.71plusminus2.10 cm3). This unique use of a replication-conditional, oncolytic virus to package a replication-incompetent amplicon vector demonstrates impressive efficacy in vitro and in vivo, and avoids the theoretical concerns of recombination with reversion to wild type.