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- Title
Development of a rapid method to generate multiple oncolytic HSV vectors and their in vivo evaluation using syngeneic mouse tumor models.
- Authors
Terada, K.; Wakimoto, H.; Tyminski, E.; Chiocca, E. A.; Saeki, Y.
- Abstract
Replication-conditional herpes simplex virus (HSV)-based vectors have great potential in the treatment of various types of cancers including brain tumors. HSV mutants lacking the UL39 gene and both copies of the γ134.5 gene (e.g. MGH1, G207) have been demonstrated to possess oncolytic effects as well as potent anticancer vaccination effects without compromising safety. Such mutants thus provide optimal templates to produce novel oncolytic HSV vectors for cancer gene therapy applications. In order to accomplish quick and efficient construction of oncolytic HSV vectors, a novel BAC-based method designated as ‘HSVQuik system’ was developed. This system sequentially utilizes two different site-specific recombination systems to introduce virtually any transgene cassettes of interest into the deleted UL39 locus (Flp-FRT in Escherichia coli) and to release the vector genome sequence from the procaryotic plasmid backbone (Cre-loxP in Vero cells). Taking advantage of the HSVQuik system, we constructed three oncolytic HSV vectors that express mouse IL4, CD40 ligand and 6CK, respectively. In vivo therapeutic experiments using two luciferase-labeled syngeneic mouse brain tumor models revealed that expression of these immunomodulators significantly enhanced antitumor efficacy of oncolytic HSV. The HSVQuik system, together with luciferase-labeled tumor models, should expedite the process of generating and evaluating oncolytic HSV vectors for cancer gene therapy applications.Gene Therapy (2006) 13, 705–714. doi:10.1038/sj.gt.3302717; published online 10 January 2006
- Subjects
HERPES simplex virus; THERAPEUTICS; RAPID methods (Microbiology); CANCER treatment; GENE therapy; ONCOGENES; VACCINATION; GENETIC engineering
- Publication
Gene Therapy, 2006, Vol 13, Issue 8, p705
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3302717