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  • Title: A novel approach to cancer therapy using an oncolytic herpes virus to package amplicons containing cytokine genes.
    Author: Carew JF, Kooby DA, Halterman MW, Kim SH, Federoff HJ, Fong Y.
    Journal: Mol Ther; 2001 Sep; 4(3):250-6. PubMed ID: 11545616.
    Abstract:
    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 (0.57+/-0.44 cm(3) versus 39.45+/-5.13 cm(3), P<0.00001), HSV-IL2 (20.97+/-4.60 cm(3)), and the G207 group (7.71+/-2.10 cm(3)). 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.
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