A novel approach to cancer therapy using an oncolytic herpes virus to package amplicons containing cytokine genes Journal Article
| Authors: | Carew, J. F.; Kooby, D. A.; Halterman, M. W.; Kim, S. H.; Federoff, H. J.; Fong, Y. |
| Article Title: | A novel approach to cancer therapy using an oncolytic herpes virus to package amplicons containing cytokine genes |
| 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 cm3 versus 39.45 ± 5.13 cm3, P < 0.00001), HSV-IL2 (20.97 ± 4.60 cm3), and the G207 group (7.71 ± 2.10 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. |
| Keywords: | cancer chemotherapy; controlled study; squamous cell carcinoma; carcinoma, squamous cell; cancer growth; nonhuman; comparative study; neoplasms; cd8-positive t-lymphocytes; animal cell; mouse; animals; mice; cell death; cell division; interleukin 2; animal experiment; animal model; in vivo study; in vitro study; tumor cells, cultured; transfection; gene transfer; animalia; cytokine; injection; immunotherapy; cancer cell; amplicon; cd4-positive t-lymphocytes; gene therapy; transgene; oncolytic virus; herpes virus; herpesviridae; simplexvirus; tumor model; immunostimulation; virus replication; herpes simplex virus; herpes; theory; interleukin-2; virus vector; dna packaging; virus infectivity; virus recombination; human herpesvirus 1; humans; article; herpes simplex virus type-1 |
| Journal Title: | Molecular Therapy |
| Volume: | 4 |
| Issue: | 3 |
| ISSN: | 1525-0016 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2001-09-01 |
| Start Page: | 250 |
| End Page: | 256 |
| Language: | English |
| DOI: | 10.1006/mthe.2001.0448 |
| PUBMED: | 11545616 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work