Antitumor efficacy of regional oncolytic viral therapy for peritoneally disseminated cancer Journal Article


Authors: Bennett, J. J.; Kooby, D. A.; Delman, K.; McAuliffe, P.; Halterman, M. W.; Federoff, H.; Fong, Y.
Article Title: Antitumor efficacy of regional oncolytic viral therapy for peritoneally disseminated cancer
Abstract: Oncolytic viral therapy is a promising new method of cancer treatment. Peritoneal dissemination of cancer is a common and fatal clinical condition seen in many malignancies, with few effective therapies available. G207, a multimutated replication-competent herpes simplex virus type-1, effectively treats disseminated peritoneal cancer. This study evaluates viral proliferation and subsequent tumoricidal effects in vitro and in vivo after regional viral delivery. In vitro studies demonstrate that G207 efficiently kills five human gastric cancer cell lines, and that permissiveness to viral replication is correlated with cytotoxicity. In a murine xenograft model of human gastric carcinomatosis, peritoneal delivery of G207 effectively kills tumor and prolongs survival. Data from quantitative PCR characterizes peritoneal clearance of virus after intraperitoneal injection, and identifies G207 replication within tumor cells in vivo, similar to in vitro proliferation. Further analysis of various organs confirms that G207 does not replicate within normal tissue after peritoneal delivery. Wild-type KOS viral replication was also demonstrated in vivo, with significant toxicity secondary to dissemination and encephalitis. In vivo viral proliferation of G207 is restricted to tumor cells, is correlated with in vitro assays, and is an important mechanism of anticancer efficacy.
Keywords: treatment outcome; human cell; disseminated cancer; polymerase chain reaction; animals; mice; peritoneal neoplasms; antineoplastic activity; tumor cells, cultured; cancer therapy; time factors; tissue distribution; mice, nude; gene therapy; oncolytic virus; stomach cancer; herpesvirus 1, human; cachexia; neoplasm transplantation; peritoneum metastasis; virus strain; herpes simplex virus; stomach neoplasms; viruses; humans; human; male; article; peritoneal tumor
Journal Title: Journal of Molecular Medicine
Volume: 78
Issue: 3
ISSN: 0946-2716
Publisher: Springer  
Date Published: 2000-05-01
Start Page: 166
End Page: 174
Language: English
PUBMED: 10868479
PROVIDER: scopus
DOI: 10.1007/s001090000092
DOI/URL:
Notes: Export Date: 18 November 2015 -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Keith Delman
    19 Delman
  2. Joseph J Bennett
    19 Bennett
  3. David Kooby
    25 Kooby
  4. Yuman Fong
    775 Fong