Multi-attenuated herpes simplex virus-1 mutant G207 exerts cytotoxicity against epithelial ovarian cancer but not normal mesothelium and is suitable for intraperitoneal oncolytic therapy.

Details

Serval ID
serval:BIB_B8BCA358D6C5
Type
Article: article from journal or magazin.
Collection
Publications
Title
Multi-attenuated herpes simplex virus-1 mutant G207 exerts cytotoxicity against epithelial ovarian cancer but not normal mesothelium and is suitable for intraperitoneal oncolytic therapy.
Journal
Cancer Gene Therapy
Author(s)
Coukos G., Makrigiannakis A., Montas S., Kaiser L.R., Toyozumi T., Benjamin I., Albelda S.M., Rubin S.C., Molnar-Kimber K.L.
ISSN
0929-1903 (Print)
ISSN-L
0929-1903
Publication state
Published
Issued date
2000
Volume
7
Number
2
Pages
275-283
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.Publication Status: ppublish
Abstract
Recombinant strains of herpes simplex virus-1 (HSV-1) harboring mutations in the infected cell product (ICP)34.5 region lose their neurovirulence and replicate more efficiently in dividing tumor cells than stationary cells, becoming replication-selective oncolytic agents. Additional mutation of the ICP6 gene, which encodes ribonucleotide reductase, further impairs the ability of HSV-1 mutants to replicate in normal cells, enhancing tumor selectivity. The present study investigated the effect of HSV-G207, a recombinant HSV-1 lacking ICP34.5 and ICP6, against epithelial ovarian cancer (EOC) in vitro and in vivo in a mouse xenograft model. To assess the selectivity of multimutated HSV-G207 against malignant cells, HSV-G207 and wild-type HSV-F were comparatively tested against normal human peritoneal mesothelial cells and EOC cells in vitro. HSV-G207 infected both EOC cells and mesothelial cells; however, unlike EOC cells, mesothelial cells provided a poor substrate for replication of HSV-G207. In contrast to wild-type HSV-F, HSV-G207 exerted a potent oncolytic effect on EOC cells but spared normal mesothelial cells in vitro. Primary EOC cells were more sensitive to the virus than established EOC cell lines. A single intraperitoneal injection of HSV-G207 resulted in a significant reduction in tumor volume and tumor spread in vivo. HSV-G207 was shown to penetrate deeply within tumor nodules and caused no apparent intraperitoneal toxicity. Oncolytic therapy with multimutated replication-restricted HSV may offer a novel approach in the treatment of EOC.
Keywords
Animals, Carcinoma/pathology, Carcinoma/therapy, Cell Transformation, Viral/genetics, DNA, Recombinant/genetics, DNA, Recombinant/metabolism, DNA, Viral/genetics, DNA, Viral/metabolism, Epithelium/virology, Female, Herpesvirus 1, Human/genetics, Herpesvirus 1, Human/pathogenicity, Humans, Infusions, Parenteral, Mice, Mice, SCID, Mutation/genetics, Ovarian Neoplasms/pathology, Ovarian Neoplasms/therapy, Tumor Cells, Cultured, Virulence, Virus Replication/genetics
Pubmed
Open Access
Yes
Create date
14/10/2014 11:42
Last modification date
20/08/2019 15:26
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