Comparison of safety, delivery, and efficacy of two oncolytic herpes viruses (G207 and NV1020) for peritoneal cancer Journal Article

Authors: Bennett, J. J.; Delman, K. A.; Burt, B. M.; Mariotti, A.; Malhotra, S.; Zager, J.; Petrowsky, H.; Mastorides, S.; Federoff, H.; Fong, Y.
Article Title: Comparison of safety, delivery, and efficacy of two oncolytic herpes viruses (G207 and NV1020) for peritoneal cancer
Abstract: G207 and NV1020 are two replication-competent, multimutant oncolytic herpes simplex viruses evaluated in the current studies for their anticancer effects in the treatment of gastric cancer. Deletion of both γ134.5 genes and inactivation of ICP6 (ribonucleotide reductase) allows G207 to selectively replicate within tumor cells. NV1020 is another attenuated recombinant herpes virus with deletions of the HSV joint region, with deletion of only one copy of the γ134.5 gene, and with the ICP6 gene intact. In vitro, both G207 and NV1020 effectively infected, replicated, and killed human gastric cancer cells, with NV1020 being more effective at lower concentrations of virus. In a murine xenograft model of peritoneally disseminated gastric cancer, both NV1020 and G207 reduced tumor burden when given intraperitoneally (i.p.) at higher doses. When viral doses were lowered or when advanced tumor was treated, i.p. NV1020 was superior to i.p. G207. In vitro viral replication and cytotoxicity predicted the in vivo antitumor response. Intravenous delivery of either G207 or NV1020 failed to reduce tumor burden, demonstrating the importance of regional therapy as treatment for compartmentalized malignancy. Both agents were safe for use in animals, and immunohistochemistry performed on mouse tissue revealed selective viral targeting of tumor. Oncolytic therapy using genetically engineered HSVs represents a promising strategy for peritoneal malignancies.
Keywords: immunohistochemistry; controlled study; disease-free survival; human cell; gene deletion; nonhuman; mouse; animals; mice; animal tissue; cell survival; peritoneum cancer; tumor volume; animal experiment; animal model; antineoplastic activity; cytotoxicity; tumor cells, cultured; cancer model; prediction; time factors; animalia; genetic engineering; xenograft; mice, nude; dna viruses; escherichia coli; gene therapy; oncolytic virus; herpesviridae; murinae; simplexvirus; transplantation, heterologous; stomach cancer; cytotoxicity, immunologic; safety; virus recombinant; virus replication; herpes simplex virus; stomach neoplasms; genetic markers; gastric cancer; ribonucleotide reductase; virus gene; virus virulence; peritoneal cancer; viral gene therapy; virulence factor; hsv; human; male; priority journal; article
Journal Title: Cancer Gene Therapy
Volume: 9
Issue: 11
ISSN: 0929-1903
Publisher: Nature Publishing Group  
Date Published: 2002-11-01
Start Page: 935
End Page: 945
Language: English
DOI: 10.1038/sj.cgt.7700510
PUBMED: 12386832
PROVIDER: scopus
Notes: Export Date: 14 November 2014 -- Source: Scopus
Citation Impact
MSK Authors
  1. Keith Delman
    19 Delman
  2. Jonathan Zager
    15 Zager
  3. Bryan M Burt
    18 Burt
  4. Joseph J Bennett
    19 Bennett
  5. Yuman Fong
    772 Fong